Juan Pineda - Academia.edu (original) (raw)

Papers by Juan Pineda

Journal of Neurophysiology, 1998

Pineda, Juan Carlos, Roberts S. Waters, and Robert C. Foehring. Specificity in the interaction of... more Pineda, Juan Carlos, Roberts S. Waters, and Robert C. Foehring. Specificity in the interaction of HVA Ca2+ channel types with Ca2+-dependent AHPs and firing behavior in neocortical pyramidal neurons. J. Neurophysiol. 79: 2522–2534, 1998. Intracellular recordings and organic and inorganic Ca2+ channel blockers were used in a neocortical brain slice preparation to test whether high-voltage–activated (HVA) Ca2+ channels are differentially coupled to Ca2+-dependent afterhyperpolarizations (AHPs) in sensorimotor neocortical pyramidal neurons. For the most part, spike repolarization was not Ca2+ dependent in these cells, although the final phase of repolarization (after the fast AHP) was sensitive to block of N-type current. Between 30 and 60% of the medium afterhyperpolarization (mAHP) and between ∼80 and 90% of the slow AHP (sAHP) were Ca2+ dependent. Based on the effects of specific organic Ca2+ channel blockers (dihydropyridines, ω-conotoxin GVIA, ω-agatoxin IVA, and ω-conotoxin MVIIC...

Biomédica, 2018

La hipótesis sobre las causas de la depresión basada en la acción de la serotonina y del sistema ... more La hipótesis sobre las causas de la depresión basada en la acción de la serotonina y del sistema inmunológico, propone que ciertos tipos de estrés distorsionan la relación entre la actividad del sistema inmunitario innato y la del sistema nervioso central.El estrés causado por una infección o el estrés psicológico excesivo activan receptores de tipo toll, como el TLR-4, el factor de transcripción NF-kB, el inflamasoma NLRP3, así como la secreción de interleucina 1 beta (IL-1β) e interleucina 6 (IL-6); esto causa, en primer lugar, los síntomas generales de enfermedad que aparecen con cualquier infección, pero también los síntomas característicos de la depresión como disforia y anhedonia.Las evidencias indican que, si el estímulo persiste o se repite en las siguientes 24 horas, se activa la enzima indolamina 2,3-dioxigenasa (IDO) de la vía metabólica de la quinurenina, lo cual incrementa la síntesis del ácido quinolínico y reduce la síntesis de serotonina. El ácido quinolínico activa ...

The neural circuits of the auditory cortex are a substrate for the dual purpose of representing a... more The neural circuits of the auditory cortex are a substrate for the dual purpose of representing and storing the auditory signal on one hand, and sending its relevant features to other cortical and subcortical areas on the other hand. The ability to process and transform the signal crucially depends on achievement of the neuronal spike threshold following spatiotemporal summation of the synaptic signals. We used patch-clamp recording in a thin slice preparation to compare neuronal responses to current injection of layer II/III and layer V neurons. We found that while the two classes of neurons do not differ in passive neuronal properties, layer II/III neurons possess a lower firing threshold relative to layer V neurons (344.8 5 2.4 mV vs. 334.3 5 4.0 mV). We speculate that a lower spiking threshold in layer II/III neurons might favor local intracolumnar activation for representation and storage of the auditory information whereas a more positive spiking threshold for layer V neurons ...

Frontiers in Synaptic Neuroscience, 2016

Berserk "Early 19th century (originally as a noun denoting a wild Norse warrior who fought with f... more Berserk "Early 19th century (originally as a noun denoting a wild Norse warrior who fought with frenzy): from Old Norse berserkr (noun), probably from birn-, bjǫrn (bear) + serkr "coat, " but also possibly from berr "bare" (i.e., without armor)." Oxford Dictionary. "His (Odin's) men rushed forwards without armor, were as mad as dogs or wolves, bit their shields, and were strong as bears or wild oxen, and killed people at a blow, but neither fire nor iron told upon them. This was called Berserkergang." Ynglinga saga and Laing Samuel (1889). The Heimskringla or the Sagas of the Norse Kings. London: John. C. Nimo. p. 276. "If a soldier survives the berserk state, it imparts emotional deadness and vulnerability to explosive rage to his psychology and permanent hyperarousal to his physiology-hallmarks of post-traumatic stress disorder in combat veterans. My clinical experience with Vietnam combat veterans prompts me to place the berserk state at the heart of their most severe psychological and psycho-physiological injuries."

The specific mechanisms by which serotonin (5-HT) modulates synaptic transmission in the auditory... more The specific mechanisms by which serotonin (5-HT) modulates synaptic transmission in the auditory cortex are still unknown. In this work, we used whole-cell recordings from layer II/III of pyramidal neurons in rat brain slices to characterize the influence of 5-HT on inhibitory synaptic activity in the auditory cortex after pharmacological blockade of excitatory glutamatergic transmission. We found that bath application of 5-HT (5 µM) reduced the frequency and amplitude of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs), reduced the amplitude of evoked IPSCs, and enhanced facilitation of paired pulse ratio (PPR), suggesting presynaptic inhibition. In order to determine whether the serotonin receptors were involved in this effect, we studied the influence of specific 5-HT receptor agonists and antagonists on ɣ-aminobutyric acid (GABA)ergic synaptic transmission. The inhibiting influence of 5-HT in the GABAergic synaptic activity was mimicked by using the selec...

Monoaminergic Modulation of Cortical Excitability, 2007

Pyramidal neurons in the sensory-motor cortex express multiple types of metabotropic receptors. S... more Pyramidal neurons in the sensory-motor cortex express multiple types of metabotropic receptors. Simultaneous application of serotonin (5-HT) and GABAB agonists produces a reduction of the neurotransmitter release probability throughout the activation of the GABAB and 5-HT1A receptors. Since some of these receptors may be coexpressed in a set of neurons, we examined the consequence of the simultaneous activation of GABAB and 5-HT receptors and investigated their influence on neurotransmitter release probability in the sensorimotor cortex of the rat using extracellular stimulation with a paired pulse protocol. We found that the effect of 5-HT is occluded when the GABAB receptor is previously activated with baclofen. The effect is mimicked by the 5-HT2 agonist DOI and prevented by the 5-HT2 antagonist ritanserine. Since prefrontal cortical 5-HT terminals may contact "en passant" fibers and release the 5-HT by volume transmission, and because 5-HT1A and 5-HT2A/C receptors are coexpressed in pyramidal neurons, they may reciprocally modify each other's metabolic pathways, leading to the production of nonlinear interactions in this cortical area. The potential implications of the cross-talk between 5-HT and GABAB receptors are discussed in terms of the consequence of the use of selective serotonin reuptake inhibitors in the treatment of the depression.

Neuroscience, 2005

The proof of your article, to be published in Neuroscience, is attached to this e-mail as a "PDF"... more The proof of your article, to be published in Neuroscience, is attached to this e-mail as a "PDF" file. You will find, in addition, a Query Form detailing any questions we have regarding your article (as a separate attachment). For helpful information on PDF files, please see the end of this e-mail.

Synapse, 2009

Spikes population evoked by a paired pulse protocol were used to assess the influence of GABA(A) ... more Spikes population evoked by a paired pulse protocol were used to assess the influence of GABA(A) and GABA(B) receptors agonists and antagonists on the synaptic potentials and in the S2/S1 ratio in a paired pulse (PP) protocol in the cortico-paleostriatum augmentatum synapses of the turtle. GABA(A) agonist, muscimol, decreased the amplitude of synaptic responses whereas the facilitation produced with the PP protocol did not change, suggesting a postsynaptic action for GABA(A) receptors. GABA(B) agonist, baclofen, enhanced paired pulse ratio indicating a presynaptic modulation through the GABA(B) receptor. Selective antagonists for N- and P/Q-type Ca(2+)-channels also enhanced paired pulse ratio, suggesting that any of these channel types may be involved in neurotransmitter release. However, the strong paired pulse facilitation produced by baclofen was occluded by blocking the N-type Ca2+ channels with omega-conotoxin GVIA (1 microM), but not by the blockage of P/Q-type Ca2+ channels with omega-agatoxin TK (400 nM). These data suggest that N and P/Q channels participate in the neurotransmitter release, whereas only N-type Ca2+ channels are involved in the presynaptic modulation of GABA(B) in the corticostriatal synapse of the turtle.

Physiology & Behavior, 2008

The interaction of caffeine (1 mg/kg) and amitriptyline (15 mg/kg) on the immobility time (IT) du... more The interaction of caffeine (1 mg/kg) and amitriptyline (15 mg/kg) on the immobility time (IT) during Porsolt's forced swimming test (FST) was investigated in female Wistar rats. Akaike's Information Criterion indicated that the ITs recorded from 142 rats during the first day of the FST followed a bimodal distribution. Hence, the median (125.5 s) was used to classify the animals in subpopulations with low (<125.5 s, LI-rats) or high (>125.5 s, HI-rats) immobility. The paired t-test was used to compare the change of ITs between the first and second swimming sessions. Vehicle-treated animals had a significant increase of ITs during the second day of the test, either in LI-rats (77+/-12 s vs. 196+/-8 s, P<0.0001, n=6) or HI-rats (150+/-8 s vs. 201+/-10 s, P<0.02, n=6). In LI-rats amitriptyline only prevented the increase of ITs during the second session (74+/-27 s vs. 97+/-42 s, n=12), whereas in HI-rats the antidepressant produced a significant decrease of ITs during the second session (161+/-22 s vs. 118+/-32 s, n=7, P<0.02). While caffeine alone prevented the increase of ITs in both groups, the methylxanthine abolished the effect of amitriptyline in HI-rats (165+/-23 s vs. 165+/-46 s, n=9), leaving the antidepressant action unaffected in LI-rats (87+/-23 s vs. 96+/-58 s, n=9). These results suggest that the anti-immobility effect of amitriptyline in HI-rats is mediated in part by endogenous adenosine.

Neuroscience Letters, 2009

Chronic caffeine consumption has been inversely associated with the risk of developing Parkinson&... more Chronic caffeine consumption has been inversely associated with the risk of developing Parkinson's disease. Here we assessed whether chronic caffeine treatment increases the resistance of male Wistar rats to haloperidol (1mg/kg, s.c.)-induced catalepsy, measured in the bar test at 15 min intervals during 3h. Caffeine (5mg/kg/day) was delivered for 6 months via drinking water. Control rats received only tap water. Treatments began when animals were 3-4 months old. In order to unveil long-lasting catalepsy refractoriness not attributable to the presence of caffeine in the brains of rats, they were evaluated from day 18 to day 27 after caffeine withdrawal, a time that is far in excess for the full excretion of a caffeine dose in this species. The average cataleptic immobility measured in caffeine-treated rats (n=23) was 1148+/-140 s, a value 34+/-8% lower than that recorded in control animals (n=20), whose mean immobility was 1736+/-137 s (P=0.0026, t-test). The percentage of catalepsy reduction measured in caffeine-treated rats evaluated on days 18-20 after caffeine discontinuation (-32+/-13%, n=12, P<0.05) was comparable to the catalepsy decrease recorded in those animals tested on days 21-27 (-36+/-10%, n=11, P<0.02), a finding compatible with the notion that the effect was indeed mediated by enduring changes of brain functioning and not by the physical presence of caffeine or its metabolites. Caffeine-treated rats also had higher catalepsy latency scores compared with control rats (P<0.01, U-test). The present findings show that chronic consumption of caffeine produces perdurable resistance to catalepsy induced by dopamine receptor blockade, possibly through enhancement of dopamine transmission, giving further support to the epidemiological results indicating that prolonged caffeine consumption affords neuroprotection against Parkinson's disease.

Neuroscience Letters, 2007

Field recordings were used to determine the influence of ␦-opioid receptor activation on corticos... more Field recordings were used to determine the influence of ␦-opioid receptor activation on corticostriatal synaptic transmission. Application of the selective ␦-opioid receptor agonist, [Tyr-D-Pen-Gly-Phe-D-Pen]-enkephalin (DPDPE, 1 M), decreased the amplitude of the field-excitatory synaptic potential and at the same time increased the paired pulse ratio (PPR) suggesting a presynaptic site of action. This response reversed rapidly when DPDPE was washed and blocked by 1 nM of the selective ␦-receptor antagonist naltrindole. Neither-conotoxin GVIA (1 M) nor-agatoxin TK (400 nM), blockers of N-and P/Q-type Ca 2+-channels, respectively, nor TEA (1 mM), blocker of some classes of K +-channels, occluded the effects of DPDPE. Instead, 1 mM 4-AP or 400 M Ba 2+ occluded completely the effects of DPDPE. Therefore, the results suggest that the modulation by ␦ opioids at corticostriatal terminals is mediated by transient (K V 4) K +-conductances.

Neuroscience, 1999

Whole-cell voltage-clamp recordings of outward currents were obtained from acutely dissociated ne... more Whole-cell voltage-clamp recordings of outward currents were obtained from acutely dissociated neurons of the rat neostriatum in conditions in which inward Ca 2+ current was not blocked and intracellular Ca 2+ concentration was lightly buffered. Na + currents were blocked with tetrodotoxin. In this situation, about 53 4% (mean S.E.M.; n=18) of the outward current evoked by a depolarization to 0 mV was sensitive to 400 µM Cd 2+. A similar percentage was sensitive to high concentrations of intracellular chelators or to extracellular Ca 2+ reduction (<500 µM); 35 4% (n=25) of the outward current was sensitive to 3.0 mM 4-aminopyridine. Most of the remaining current was blocked by 10 mM tetraethylammonium. The results suggest that about half of the outward current is activated by Ca 2+ entry in the present conditions. The peptidic toxins charybdotoxin, iberotoxin and apamin confirmed these results, since 34 5% (n=14), 29 5% (n=14) and 28 6% (n=9) of the outward current was blocked by these peptides, respectively. The effects of charybdotoxin and iberotoxin added to that of apamin, but their effects largely occluded each other. There was additional Cd 2+ block after the effect of any combination of toxins. Therefore, it is concluded that Ca 2+-activated outward currents in neostriatal neurons comprise several components, including small and large conductance types. In addition, the present experiments demonstrate that Ca 2+-activated K + currents are a very important component of the outward current activated by depolarization in neostriatal neurons. 1998 IBRO. Published by Elsevier Science Ltd.

NeuroReport, 1999

Intracellular recordings in an in vitro neocortical slice preparation from immature rats were use... more Intracellular recordings in an in vitro neocortical slice preparation from immature rats were used to investigate the Ca2 source for slow afterhyperpolarization (sAHP) generation in pyramidal neurons that exhibit complete spike frequency adaptation (CA neurons). In pyramidal neurons that maintain repetitive firing for long periods of time (RF neurons), N-, P- and Q-type Ca2+ channels supply Ca2+ for sAHP generation. In CA neurons, the sAHP was reduced by only 50% by the combination of antagonists for these Ca2+ channel types and L-type channels. Ryanodine and dantrolene, blockers of Ca2(+)-induced Ca2+ release, reduced the sAHP by approximately 45% in CA neurons, but caused no reduction of the sAHP in RF neurons. Dantrolene application caused CA neurons to fire throughout a 1s suprathreshold current injection (as do RF neurons).

Neuropharmacology, 2003

The possible synergism between caffeine and muscarinic antagonists to inhibit haloperidol-induced... more The possible synergism between caffeine and muscarinic antagonists to inhibit haloperidol-induced catalepsy was investigated with the bar test in rats. Pretreatment with low doses of caffeine (1-3 mg/kg), a non-selective adenosine antagonist, dose dependently reduced the intensity and increased the onset latency of catalepsy induced by haloperidol (0.5-2 mg/kg). Similar effects were produced by the muscarinic antagonists atropine (4.1 mg/kg), and trihexyphenidyl (THP, 0.01-3 mg/kg). THP inhibited catalepsy intensity with an ED 50 of 0.38 mg/kg, and increased its onset latency with an ED 50 of 0.52 mg/kg. The anticataleptic effect of anticholinergics was potentiated when a low dose of caffeine (1 mg/kg) was applied simultaneously. In the presence of caffeine, THP inhibited catalepsy intensity with an ED 50 of 0.19 mg/kg, and prolonged the latency with an ED 50 of 0.30 mg/kg. The synergism was more evident when THP was administered at subthreshold doses that were unable to modify haloperidol-induced catalepsy when applied alone, but produced a clear inhibition of catalepsy when injected with caffeine. To assess whether repeated administration of caffeine could induce tolerance to the synergism with THP, a group of rats was pretreated with three daily doses of caffeine (1 mg/kg) for seven days, and the catalepsy test was performed on the eighth day. In these animals, caffeine was still able to enhance the anticataleptic actions of THP, suggesting that repeated administration of 1 mg/kg caffeine does not induce tolerance to the synergism with anticholinergics. These results indicate that low doses of caffeine enhance the anticataleptic actions of muscarinic antagonists, and leave open the possibility of using caffeine as adjunctive therapy to reduce the doses and the adverse effects of anticholinergics in Parkinson's disease.

Journal of Neuroscience Research, 2004

Activation of gamma-aminobutyric acid B (GABA(B)) and 5-hydroxytryptamine (5-HT) receptors produc... more Activation of gamma-aminobutyric acid B (GABA(B)) and 5-hydroxytryptamine (5-HT) receptors produces presynaptic inhibition at glutamatergic terminals in the rat neocortex. To evaluate interactions between these metabotropic receptors, field potentials were recorded in layer 2/3 of somatosensory cortex. In addition, the paired pulse (PP) protocol was used to measure changes in the ratio of the second/first extracellular synaptic potentials (S(2)/S(1) ratio) as an index of glutamate release probability in the area. Lowering extracellular [Ca(2+)](o) to 0.5 mM, increased the S(2)/S(1) ratio by 318 +/- 134%. 5-HT (1 microM) increased the S(2)/S(1) ratio by 61 +/- 15%. In presence of the GABA(A) antagonist bicuculline (10 microM), 5-HT increased the S(2)/S(1) ratio by 98 +/- 15%. This effect did not desensitize after two consecutive applications of the amine, and was dose dependent in the concentration range between 0.03-1 microM (EC(50) = 2.36 x 10(-7) mol/L). The increase of S(2)/S(1) ratio induced by 5-HT (1 microM) was blocked reversibly by the 5-HT(1A) antagonist NAN-190 (10-30 microM), but was unaffected by the selective GABA(B) antagonist CGP 52432 (1 microM). The action of 5-HT was mimicked by the 5-HT(1A/7) agonist 8OH-DPAT (10 microM), increasing the S(2)/S(1) ratio by 84 +/- 2%, a response that was unaffected by the 5-HT(2/7) antagonist ritanserin (2 microM). The 5-HT(1B) agonist CP93129 (10 microM) had no effect. The GABA(B) agonist baclofen (1 microM) increased the S(2)/S(1) ratio up to 308 +/- 33%, which is similar to that produced by low [Ca(2+)](o). When the effect of baclofen was maximal, application of 5-HT (1 microM) reversed the S(2)/S(1) ratio back to 78 +/- 27%, a result that was blocked by the 5-HT(2/7) antagonist ritanserin (100 nM). Notably, the interaction between the GABA(B) agonist and 5-HT was order dependent, because enhancement of the S(2)/S(1) ratio elicited by baclofen was not inhibited if 5-HT was applied first. These results suggest a complex interaction between GABA(B), 5-HT(1A), and 5-HT(2) receptors in layer 2/3 of rat somatosensory cortex. Activation of GABA(B) receptors induces PP facilitation (inhibits glutamate release) more efficiently than does activation of 5-HT(1A) receptors. When the effect of GABA(B) receptor activation is maximal, however, the influence of 5-HT changes to the opposite direction, inhibiting PP facilitation (increasing glutamate release) through activation of 5-HT(2) receptors.

Journal of Neuroscience Methods, 2005

Catalepsy tests performed in rodents treated with drugs that interfere with dopaminergic transmis... more Catalepsy tests performed in rodents treated with drugs that interfere with dopaminergic transmission have been widely used for the screening of drugs with therapeutic potential in the treatment of Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. The basic method for measuring catalepsy intensity is the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;standard&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; bar test. We present here an easy to use microcontroller-based automatic system for recording bar test experiments. The design is simple, compact, and has a low cost. Recording intervals and total experimental time can be programmed within a wide range of values. The resulting catalepsy times are stored, and up to five simultaneous experiments can be recorded. A standard personal computer interface is included. The automated system also permits the elimination of human error associated with factors such as fatigue, distraction, and data transcription, occurring during manual recording. Furthermore, a uniform criterion for timing the cataleptic condition can be achieved. Correlation values between the results obtained with the automated system and those reported by two independent observers ranged between 0.88 and 0.99 (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001; three treatments, nine animals, 144 catalepsy time measurements).

Hearing Research, 2004

The neural circuits of the auditory cortex are a substrate for the dual purpose of representing a... more The neural circuits of the auditory cortex are a substrate for the dual purpose of representing and storing the auditory signal on one hand, and sending its relevant features to other cortical and subcortical areas on the other hand. The ability to process and transform the signal crucially depends on achievement of the neuronal spike threshold following spatiotemporal summation of the synaptic signals. We used patch-clamp recording in a thin slice preparation to compare neuronal responses to current injection of layer II/III and layer V neurons. We found that while the two classes of neurons do not differ in passive neuronal properties, layer II/III neurons possess a lower firing threshold relative to layer V neurons (-44.8 +/- 2.4 mV vs. -34.3 +/- 4.0 mV). We speculate that a lower spiking threshold in layer II/III neurons might favor local intracolumnar activation for representation and storage of the auditory information whereas a more positive spiking threshold for layer V neurons may prevent unnecessary cortical spread of a scarcely processed signal.

European Journal of Pharmacology, 2001

To know which Ca(2+) channel type is the most important for neurotransmitter release at corticost... more To know which Ca(2+) channel type is the most important for neurotransmitter release at corticostriatal synapses of the rat, we tested Ca(2+) channel antagonists on the paired pulse ratio. omega-Agatoxin TK was the most effective Ca(2+) channel antagonist (IC(50)=127 nM; maximal effect=211% (with &gt;1 microM) and Hill coefficient=1.2), suggesting a single site of action and a Q-type channel profile. Corresponding parameters for Cd(2+) were 13 microM, 178% and 1.2. The block of L-type Ca(2+) channels had little impact on transmission, but we also tested facilitation of L-type Ca(2+) channels. The L-type Ca(2+) channel agonist, s-(-)-1,4 dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridine carboxylic acid methyl ester (Bay K 8644 (5 microM)), produced a 45% reduction of the paired pulse ratio, suggesting that even if L-type channels do not participate in the release process, they may participate in its modulation.

European Journal of Pharmacology, 1995

The actions of carbachol were studied on the firing response of neostriatal neurons recorded intr... more The actions of carbachol were studied on the firing response of neostriatal neurons recorded intracellularly from in vitro slice preparations of the rat brain. Carbachol (1-10 ixM) reversibly reduced the afterhyperpolarization in neostriatal neurons. This effect was accompanied by an increase in both firing frequency and input resistance in the subthreshold voltage range. Atropine (1-10 ~zM) reversibly blocked carbachol effects, suggesting muscarinic receptor modulation. Pirenzepine (up to 1 /xM), but not AF-DX 384 (10 txM) or gallamine (30 txM), blocked the effects of carbachol on the afterhyperpolarization. The protein kinase C activator, phorbol 12,13 dibutyrate, but not the inactive phorbol ester, 4a-phorbol 12-myristate 13-acetate, mimicked carbachol effects. The results suggest that muscarinic receptors, probably of the M 1 type, regulate neostriatal excitability by modulating afterhyperpolarization.

Journal of Neurophysiology, 1998

Pineda, Juan Carlos, Roberts S. Waters, and Robert C. Foehring. Specificity in the interaction of... more Pineda, Juan Carlos, Roberts S. Waters, and Robert C. Foehring. Specificity in the interaction of HVA Ca2+ channel types with Ca2+-dependent AHPs and firing behavior in neocortical pyramidal neurons. J. Neurophysiol. 79: 2522–2534, 1998. Intracellular recordings and organic and inorganic Ca2+ channel blockers were used in a neocortical brain slice preparation to test whether high-voltage–activated (HVA) Ca2+ channels are differentially coupled to Ca2+-dependent afterhyperpolarizations (AHPs) in sensorimotor neocortical pyramidal neurons. For the most part, spike repolarization was not Ca2+ dependent in these cells, although the final phase of repolarization (after the fast AHP) was sensitive to block of N-type current. Between 30 and 60% of the medium afterhyperpolarization (mAHP) and between ∼80 and 90% of the slow AHP (sAHP) were Ca2+ dependent. Based on the effects of specific organic Ca2+ channel blockers (dihydropyridines, ω-conotoxin GVIA, ω-agatoxin IVA, and ω-conotoxin MVIIC...

Biomédica, 2018

La hipótesis sobre las causas de la depresión basada en la acción de la serotonina y del sistema ... more La hipótesis sobre las causas de la depresión basada en la acción de la serotonina y del sistema inmunológico, propone que ciertos tipos de estrés distorsionan la relación entre la actividad del sistema inmunitario innato y la del sistema nervioso central.El estrés causado por una infección o el estrés psicológico excesivo activan receptores de tipo toll, como el TLR-4, el factor de transcripción NF-kB, el inflamasoma NLRP3, así como la secreción de interleucina 1 beta (IL-1β) e interleucina 6 (IL-6); esto causa, en primer lugar, los síntomas generales de enfermedad que aparecen con cualquier infección, pero también los síntomas característicos de la depresión como disforia y anhedonia.Las evidencias indican que, si el estímulo persiste o se repite en las siguientes 24 horas, se activa la enzima indolamina 2,3-dioxigenasa (IDO) de la vía metabólica de la quinurenina, lo cual incrementa la síntesis del ácido quinolínico y reduce la síntesis de serotonina. El ácido quinolínico activa ...

The neural circuits of the auditory cortex are a substrate for the dual purpose of representing a... more The neural circuits of the auditory cortex are a substrate for the dual purpose of representing and storing the auditory signal on one hand, and sending its relevant features to other cortical and subcortical areas on the other hand. The ability to process and transform the signal crucially depends on achievement of the neuronal spike threshold following spatiotemporal summation of the synaptic signals. We used patch-clamp recording in a thin slice preparation to compare neuronal responses to current injection of layer II/III and layer V neurons. We found that while the two classes of neurons do not differ in passive neuronal properties, layer II/III neurons possess a lower firing threshold relative to layer V neurons (344.8 5 2.4 mV vs. 334.3 5 4.0 mV). We speculate that a lower spiking threshold in layer II/III neurons might favor local intracolumnar activation for representation and storage of the auditory information whereas a more positive spiking threshold for layer V neurons ...

Frontiers in Synaptic Neuroscience, 2016

Berserk "Early 19th century (originally as a noun denoting a wild Norse warrior who fought with f... more Berserk "Early 19th century (originally as a noun denoting a wild Norse warrior who fought with frenzy): from Old Norse berserkr (noun), probably from birn-, bjǫrn (bear) + serkr "coat, " but also possibly from berr "bare" (i.e., without armor)." Oxford Dictionary. "His (Odin's) men rushed forwards without armor, were as mad as dogs or wolves, bit their shields, and were strong as bears or wild oxen, and killed people at a blow, but neither fire nor iron told upon them. This was called Berserkergang." Ynglinga saga and Laing Samuel (1889). The Heimskringla or the Sagas of the Norse Kings. London: John. C. Nimo. p. 276. "If a soldier survives the berserk state, it imparts emotional deadness and vulnerability to explosive rage to his psychology and permanent hyperarousal to his physiology-hallmarks of post-traumatic stress disorder in combat veterans. My clinical experience with Vietnam combat veterans prompts me to place the berserk state at the heart of their most severe psychological and psycho-physiological injuries."

The specific mechanisms by which serotonin (5-HT) modulates synaptic transmission in the auditory... more The specific mechanisms by which serotonin (5-HT) modulates synaptic transmission in the auditory cortex are still unknown. In this work, we used whole-cell recordings from layer II/III of pyramidal neurons in rat brain slices to characterize the influence of 5-HT on inhibitory synaptic activity in the auditory cortex after pharmacological blockade of excitatory glutamatergic transmission. We found that bath application of 5-HT (5 µM) reduced the frequency and amplitude of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs), reduced the amplitude of evoked IPSCs, and enhanced facilitation of paired pulse ratio (PPR), suggesting presynaptic inhibition. In order to determine whether the serotonin receptors were involved in this effect, we studied the influence of specific 5-HT receptor agonists and antagonists on ɣ-aminobutyric acid (GABA)ergic synaptic transmission. The inhibiting influence of 5-HT in the GABAergic synaptic activity was mimicked by using the selec...

Monoaminergic Modulation of Cortical Excitability, 2007

Pyramidal neurons in the sensory-motor cortex express multiple types of metabotropic receptors. S... more Pyramidal neurons in the sensory-motor cortex express multiple types of metabotropic receptors. Simultaneous application of serotonin (5-HT) and GABAB agonists produces a reduction of the neurotransmitter release probability throughout the activation of the GABAB and 5-HT1A receptors. Since some of these receptors may be coexpressed in a set of neurons, we examined the consequence of the simultaneous activation of GABAB and 5-HT receptors and investigated their influence on neurotransmitter release probability in the sensorimotor cortex of the rat using extracellular stimulation with a paired pulse protocol. We found that the effect of 5-HT is occluded when the GABAB receptor is previously activated with baclofen. The effect is mimicked by the 5-HT2 agonist DOI and prevented by the 5-HT2 antagonist ritanserine. Since prefrontal cortical 5-HT terminals may contact "en passant" fibers and release the 5-HT by volume transmission, and because 5-HT1A and 5-HT2A/C receptors are coexpressed in pyramidal neurons, they may reciprocally modify each other's metabolic pathways, leading to the production of nonlinear interactions in this cortical area. The potential implications of the cross-talk between 5-HT and GABAB receptors are discussed in terms of the consequence of the use of selective serotonin reuptake inhibitors in the treatment of the depression.

Neuroscience, 2005

The proof of your article, to be published in Neuroscience, is attached to this e-mail as a "PDF"... more The proof of your article, to be published in Neuroscience, is attached to this e-mail as a "PDF" file. You will find, in addition, a Query Form detailing any questions we have regarding your article (as a separate attachment). For helpful information on PDF files, please see the end of this e-mail.

Synapse, 2009

Spikes population evoked by a paired pulse protocol were used to assess the influence of GABA(A) ... more Spikes population evoked by a paired pulse protocol were used to assess the influence of GABA(A) and GABA(B) receptors agonists and antagonists on the synaptic potentials and in the S2/S1 ratio in a paired pulse (PP) protocol in the cortico-paleostriatum augmentatum synapses of the turtle. GABA(A) agonist, muscimol, decreased the amplitude of synaptic responses whereas the facilitation produced with the PP protocol did not change, suggesting a postsynaptic action for GABA(A) receptors. GABA(B) agonist, baclofen, enhanced paired pulse ratio indicating a presynaptic modulation through the GABA(B) receptor. Selective antagonists for N- and P/Q-type Ca(2+)-channels also enhanced paired pulse ratio, suggesting that any of these channel types may be involved in neurotransmitter release. However, the strong paired pulse facilitation produced by baclofen was occluded by blocking the N-type Ca2+ channels with omega-conotoxin GVIA (1 microM), but not by the blockage of P/Q-type Ca2+ channels with omega-agatoxin TK (400 nM). These data suggest that N and P/Q channels participate in the neurotransmitter release, whereas only N-type Ca2+ channels are involved in the presynaptic modulation of GABA(B) in the corticostriatal synapse of the turtle.

Physiology & Behavior, 2008

The interaction of caffeine (1 mg/kg) and amitriptyline (15 mg/kg) on the immobility time (IT) du... more The interaction of caffeine (1 mg/kg) and amitriptyline (15 mg/kg) on the immobility time (IT) during Porsolt&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s forced swimming test (FST) was investigated in female Wistar rats. Akaike&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Information Criterion indicated that the ITs recorded from 142 rats during the first day of the FST followed a bimodal distribution. Hence, the median (125.5 s) was used to classify the animals in subpopulations with low (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;125.5 s, LI-rats) or high (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;125.5 s, HI-rats) immobility. The paired t-test was used to compare the change of ITs between the first and second swimming sessions. Vehicle-treated animals had a significant increase of ITs during the second day of the test, either in LI-rats (77+/-12 s vs. 196+/-8 s, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001, n=6) or HI-rats (150+/-8 s vs. 201+/-10 s, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.02, n=6). In LI-rats amitriptyline only prevented the increase of ITs during the second session (74+/-27 s vs. 97+/-42 s, n=12), whereas in HI-rats the antidepressant produced a significant decrease of ITs during the second session (161+/-22 s vs. 118+/-32 s, n=7, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.02). While caffeine alone prevented the increase of ITs in both groups, the methylxanthine abolished the effect of amitriptyline in HI-rats (165+/-23 s vs. 165+/-46 s, n=9), leaving the antidepressant action unaffected in LI-rats (87+/-23 s vs. 96+/-58 s, n=9). These results suggest that the anti-immobility effect of amitriptyline in HI-rats is mediated in part by endogenous adenosine.

Neuroscience Letters, 2009

Chronic caffeine consumption has been inversely associated with the risk of developing Parkinson&... more Chronic caffeine consumption has been inversely associated with the risk of developing Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. Here we assessed whether chronic caffeine treatment increases the resistance of male Wistar rats to haloperidol (1mg/kg, s.c.)-induced catalepsy, measured in the bar test at 15 min intervals during 3h. Caffeine (5mg/kg/day) was delivered for 6 months via drinking water. Control rats received only tap water. Treatments began when animals were 3-4 months old. In order to unveil long-lasting catalepsy refractoriness not attributable to the presence of caffeine in the brains of rats, they were evaluated from day 18 to day 27 after caffeine withdrawal, a time that is far in excess for the full excretion of a caffeine dose in this species. The average cataleptic immobility measured in caffeine-treated rats (n=23) was 1148+/-140 s, a value 34+/-8% lower than that recorded in control animals (n=20), whose mean immobility was 1736+/-137 s (P=0.0026, t-test). The percentage of catalepsy reduction measured in caffeine-treated rats evaluated on days 18-20 after caffeine discontinuation (-32+/-13%, n=12, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05) was comparable to the catalepsy decrease recorded in those animals tested on days 21-27 (-36+/-10%, n=11, P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.02), a finding compatible with the notion that the effect was indeed mediated by enduring changes of brain functioning and not by the physical presence of caffeine or its metabolites. Caffeine-treated rats also had higher catalepsy latency scores compared with control rats (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01, U-test). The present findings show that chronic consumption of caffeine produces perdurable resistance to catalepsy induced by dopamine receptor blockade, possibly through enhancement of dopamine transmission, giving further support to the epidemiological results indicating that prolonged caffeine consumption affords neuroprotection against Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease.

Neuroscience Letters, 2007

Field recordings were used to determine the influence of ␦-opioid receptor activation on corticos... more Field recordings were used to determine the influence of ␦-opioid receptor activation on corticostriatal synaptic transmission. Application of the selective ␦-opioid receptor agonist, [Tyr-D-Pen-Gly-Phe-D-Pen]-enkephalin (DPDPE, 1 M), decreased the amplitude of the field-excitatory synaptic potential and at the same time increased the paired pulse ratio (PPR) suggesting a presynaptic site of action. This response reversed rapidly when DPDPE was washed and blocked by 1 nM of the selective ␦-receptor antagonist naltrindole. Neither-conotoxin GVIA (1 M) nor-agatoxin TK (400 nM), blockers of N-and P/Q-type Ca 2+-channels, respectively, nor TEA (1 mM), blocker of some classes of K +-channels, occluded the effects of DPDPE. Instead, 1 mM 4-AP or 400 M Ba 2+ occluded completely the effects of DPDPE. Therefore, the results suggest that the modulation by ␦ opioids at corticostriatal terminals is mediated by transient (K V 4) K +-conductances.

Neuroscience, 1999

Whole-cell voltage-clamp recordings of outward currents were obtained from acutely dissociated ne... more Whole-cell voltage-clamp recordings of outward currents were obtained from acutely dissociated neurons of the rat neostriatum in conditions in which inward Ca 2+ current was not blocked and intracellular Ca 2+ concentration was lightly buffered. Na + currents were blocked with tetrodotoxin. In this situation, about 53 4% (mean S.E.M.; n=18) of the outward current evoked by a depolarization to 0 mV was sensitive to 400 µM Cd 2+. A similar percentage was sensitive to high concentrations of intracellular chelators or to extracellular Ca 2+ reduction (<500 µM); 35 4% (n=25) of the outward current was sensitive to 3.0 mM 4-aminopyridine. Most of the remaining current was blocked by 10 mM tetraethylammonium. The results suggest that about half of the outward current is activated by Ca 2+ entry in the present conditions. The peptidic toxins charybdotoxin, iberotoxin and apamin confirmed these results, since 34 5% (n=14), 29 5% (n=14) and 28 6% (n=9) of the outward current was blocked by these peptides, respectively. The effects of charybdotoxin and iberotoxin added to that of apamin, but their effects largely occluded each other. There was additional Cd 2+ block after the effect of any combination of toxins. Therefore, it is concluded that Ca 2+-activated outward currents in neostriatal neurons comprise several components, including small and large conductance types. In addition, the present experiments demonstrate that Ca 2+-activated K + currents are a very important component of the outward current activated by depolarization in neostriatal neurons. 1998 IBRO. Published by Elsevier Science Ltd.

NeuroReport, 1999

Intracellular recordings in an in vitro neocortical slice preparation from immature rats were use... more Intracellular recordings in an in vitro neocortical slice preparation from immature rats were used to investigate the Ca2 source for slow afterhyperpolarization (sAHP) generation in pyramidal neurons that exhibit complete spike frequency adaptation (CA neurons). In pyramidal neurons that maintain repetitive firing for long periods of time (RF neurons), N-, P- and Q-type Ca2+ channels supply Ca2+ for sAHP generation. In CA neurons, the sAHP was reduced by only 50% by the combination of antagonists for these Ca2+ channel types and L-type channels. Ryanodine and dantrolene, blockers of Ca2(+)-induced Ca2+ release, reduced the sAHP by approximately 45% in CA neurons, but caused no reduction of the sAHP in RF neurons. Dantrolene application caused CA neurons to fire throughout a 1s suprathreshold current injection (as do RF neurons).

Neuropharmacology, 2003

The possible synergism between caffeine and muscarinic antagonists to inhibit haloperidol-induced... more The possible synergism between caffeine and muscarinic antagonists to inhibit haloperidol-induced catalepsy was investigated with the bar test in rats. Pretreatment with low doses of caffeine (1-3 mg/kg), a non-selective adenosine antagonist, dose dependently reduced the intensity and increased the onset latency of catalepsy induced by haloperidol (0.5-2 mg/kg). Similar effects were produced by the muscarinic antagonists atropine (4.1 mg/kg), and trihexyphenidyl (THP, 0.01-3 mg/kg). THP inhibited catalepsy intensity with an ED 50 of 0.38 mg/kg, and increased its onset latency with an ED 50 of 0.52 mg/kg. The anticataleptic effect of anticholinergics was potentiated when a low dose of caffeine (1 mg/kg) was applied simultaneously. In the presence of caffeine, THP inhibited catalepsy intensity with an ED 50 of 0.19 mg/kg, and prolonged the latency with an ED 50 of 0.30 mg/kg. The synergism was more evident when THP was administered at subthreshold doses that were unable to modify haloperidol-induced catalepsy when applied alone, but produced a clear inhibition of catalepsy when injected with caffeine. To assess whether repeated administration of caffeine could induce tolerance to the synergism with THP, a group of rats was pretreated with three daily doses of caffeine (1 mg/kg) for seven days, and the catalepsy test was performed on the eighth day. In these animals, caffeine was still able to enhance the anticataleptic actions of THP, suggesting that repeated administration of 1 mg/kg caffeine does not induce tolerance to the synergism with anticholinergics. These results indicate that low doses of caffeine enhance the anticataleptic actions of muscarinic antagonists, and leave open the possibility of using caffeine as adjunctive therapy to reduce the doses and the adverse effects of anticholinergics in Parkinson's disease.

Journal of Neuroscience Research, 2004

Activation of gamma-aminobutyric acid B (GABA(B)) and 5-hydroxytryptamine (5-HT) receptors produc... more Activation of gamma-aminobutyric acid B (GABA(B)) and 5-hydroxytryptamine (5-HT) receptors produces presynaptic inhibition at glutamatergic terminals in the rat neocortex. To evaluate interactions between these metabotropic receptors, field potentials were recorded in layer 2/3 of somatosensory cortex. In addition, the paired pulse (PP) protocol was used to measure changes in the ratio of the second/first extracellular synaptic potentials (S(2)/S(1) ratio) as an index of glutamate release probability in the area. Lowering extracellular [Ca(2+)](o) to 0.5 mM, increased the S(2)/S(1) ratio by 318 +/- 134%. 5-HT (1 microM) increased the S(2)/S(1) ratio by 61 +/- 15%. In presence of the GABA(A) antagonist bicuculline (10 microM), 5-HT increased the S(2)/S(1) ratio by 98 +/- 15%. This effect did not desensitize after two consecutive applications of the amine, and was dose dependent in the concentration range between 0.03-1 microM (EC(50) = 2.36 x 10(-7) mol/L). The increase of S(2)/S(1) ratio induced by 5-HT (1 microM) was blocked reversibly by the 5-HT(1A) antagonist NAN-190 (10-30 microM), but was unaffected by the selective GABA(B) antagonist CGP 52432 (1 microM). The action of 5-HT was mimicked by the 5-HT(1A/7) agonist 8OH-DPAT (10 microM), increasing the S(2)/S(1) ratio by 84 +/- 2%, a response that was unaffected by the 5-HT(2/7) antagonist ritanserin (2 microM). The 5-HT(1B) agonist CP93129 (10 microM) had no effect. The GABA(B) agonist baclofen (1 microM) increased the S(2)/S(1) ratio up to 308 +/- 33%, which is similar to that produced by low [Ca(2+)](o). When the effect of baclofen was maximal, application of 5-HT (1 microM) reversed the S(2)/S(1) ratio back to 78 +/- 27%, a result that was blocked by the 5-HT(2/7) antagonist ritanserin (100 nM). Notably, the interaction between the GABA(B) agonist and 5-HT was order dependent, because enhancement of the S(2)/S(1) ratio elicited by baclofen was not inhibited if 5-HT was applied first. These results suggest a complex interaction between GABA(B), 5-HT(1A), and 5-HT(2) receptors in layer 2/3 of rat somatosensory cortex. Activation of GABA(B) receptors induces PP facilitation (inhibits glutamate release) more efficiently than does activation of 5-HT(1A) receptors. When the effect of GABA(B) receptor activation is maximal, however, the influence of 5-HT changes to the opposite direction, inhibiting PP facilitation (increasing glutamate release) through activation of 5-HT(2) receptors.

Journal of Neuroscience Methods, 2005

Catalepsy tests performed in rodents treated with drugs that interfere with dopaminergic transmis... more Catalepsy tests performed in rodents treated with drugs that interfere with dopaminergic transmission have been widely used for the screening of drugs with therapeutic potential in the treatment of Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. The basic method for measuring catalepsy intensity is the &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;standard&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; bar test. We present here an easy to use microcontroller-based automatic system for recording bar test experiments. The design is simple, compact, and has a low cost. Recording intervals and total experimental time can be programmed within a wide range of values. The resulting catalepsy times are stored, and up to five simultaneous experiments can be recorded. A standard personal computer interface is included. The automated system also permits the elimination of human error associated with factors such as fatigue, distraction, and data transcription, occurring during manual recording. Furthermore, a uniform criterion for timing the cataleptic condition can be achieved. Correlation values between the results obtained with the automated system and those reported by two independent observers ranged between 0.88 and 0.99 (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001; three treatments, nine animals, 144 catalepsy time measurements).

Hearing Research, 2004

The neural circuits of the auditory cortex are a substrate for the dual purpose of representing a... more The neural circuits of the auditory cortex are a substrate for the dual purpose of representing and storing the auditory signal on one hand, and sending its relevant features to other cortical and subcortical areas on the other hand. The ability to process and transform the signal crucially depends on achievement of the neuronal spike threshold following spatiotemporal summation of the synaptic signals. We used patch-clamp recording in a thin slice preparation to compare neuronal responses to current injection of layer II/III and layer V neurons. We found that while the two classes of neurons do not differ in passive neuronal properties, layer II/III neurons possess a lower firing threshold relative to layer V neurons (-44.8 +/- 2.4 mV vs. -34.3 +/- 4.0 mV). We speculate that a lower spiking threshold in layer II/III neurons might favor local intracolumnar activation for representation and storage of the auditory information whereas a more positive spiking threshold for layer V neurons may prevent unnecessary cortical spread of a scarcely processed signal.

European Journal of Pharmacology, 2001

To know which Ca(2+) channel type is the most important for neurotransmitter release at corticost... more To know which Ca(2+) channel type is the most important for neurotransmitter release at corticostriatal synapses of the rat, we tested Ca(2+) channel antagonists on the paired pulse ratio. omega-Agatoxin TK was the most effective Ca(2+) channel antagonist (IC(50)=127 nM; maximal effect=211% (with &gt;1 microM) and Hill coefficient=1.2), suggesting a single site of action and a Q-type channel profile. Corresponding parameters for Cd(2+) were 13 microM, 178% and 1.2. The block of L-type Ca(2+) channels had little impact on transmission, but we also tested facilitation of L-type Ca(2+) channels. The L-type Ca(2+) channel agonist, s-(-)-1,4 dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridine carboxylic acid methyl ester (Bay K 8644 (5 microM)), produced a 45% reduction of the paired pulse ratio, suggesting that even if L-type channels do not participate in the release process, they may participate in its modulation.

European Journal of Pharmacology, 1995

The actions of carbachol were studied on the firing response of neostriatal neurons recorded intr... more The actions of carbachol were studied on the firing response of neostriatal neurons recorded intracellularly from in vitro slice preparations of the rat brain. Carbachol (1-10 ixM) reversibly reduced the afterhyperpolarization in neostriatal neurons. This effect was accompanied by an increase in both firing frequency and input resistance in the subthreshold voltage range. Atropine (1-10 ~zM) reversibly blocked carbachol effects, suggesting muscarinic receptor modulation. Pirenzepine (up to 1 /xM), but not AF-DX 384 (10 txM) or gallamine (30 txM), blocked the effects of carbachol on the afterhyperpolarization. The protein kinase C activator, phorbol 12,13 dibutyrate, but not the inactive phorbol ester, 4a-phorbol 12-myristate 13-acetate, mimicked carbachol effects. The results suggest that muscarinic receptors, probably of the M 1 type, regulate neostriatal excitability by modulating afterhyperpolarization.