R. Foehring | University of Tennessee Health Science Center (original) (raw)

Papers by R. Foehring

Research paper thumbnail of Dynamics in Gonadotropin-Releasing Hormone Neurons Two Slow Calcium-Activated Afterhyperpolarization Currents Control Burst Firing

(PDF) (Full Text) (Abstract)

Research paper thumbnail of Opposing Influences on cAMP Response Element-Binding Protein Estradiol Activates Group I and II Metabotropic Glutamate Receptor Signaling, Leading to

Sayer, Rod J. Group I metabotropic glutamate receptors mediate a role in autoinhibition of transm... more Sayer, Rod J. Group I metabotropic glutamate receptors mediate a role in autoinhibition of transmitter release (reviewed by slow inhibition of calcium current in neocortical neurons J. Neuro-Stefani et al. 1996b). mGluR subtypes are encoded by eight physiol. 80: 1981-1988, 1998. Metabotropic glutamate receptor known genes and are classified into three groups based on (mGluR)-mediated inhibition of high-voltage-activated Ca 2/ curamino acid sequence similarities and pharmacology: group rents was investigated in pyramidal neurons acutely isolated from I, mGluR1 and mGluR5; group II, mGluR2 and mGluR3; rat dorsal frontoparietal neocortex. Whole cell recordings were and group III, mGluR4, mGluR6, mGluR7, and mGluR8. made at 30-32ЊC, with Ca 2/ as the charge carrier. Selective ago-Splice variants have been found for several mGluR subtypes nists were used to classify the subgroup of mGluRs mediating the (for a review of mGluR classification and pharmacology see response. Ca 2/ currents were inhibited by (1S,3R)-1-aminocyclo-Conn and Pin 1997). Recent studies used selective agonists pentane-1,3-dicarboxylic acid (1S,3R-ACPD) and by the group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) but not by the to identify which groups of mGluRs are involved in Ca 2/ group II agonist (2S,2R,3R)-2-(2,3-dicarboxycyclopropyl)channel regulation. In neocortical pyramidal neurons, recepglycine (DCG-IV) or the group III agonist L (/)-2-amino-4-phostors from all three groups have been implicated; Ca 2/ chanphonobutryic acid (L-AP4). (2S,1S,2S)-2-(carboxycyclopropyl)nel inhibition was observed in response to the group I agonist glycine (L-CCG-I) was effective at 10 and 100 mM but not at 1 (RS)-3,5-dihydroxyphenylglycine (DHPG) and the group mM, consistent with involvement of group I mGluRs. Variable II agonist (2S,2R,3R)-2-(2,3-dicarboxycyclopropyl)results were obtained with the putative mGluR5-selective agonist glycine (DCG-IV) (Choi and Lovinger 1996) and also to (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) and the putative L (/)-2-amino-4-phosphonobutyric acid (L-AP4), a group mGluR1-selective antagonist (S)-4-carboxyphenylglycine [(S)-III agonist (Stefani et al. 1996a 1998). The Ca 2/ channel 4CPG], indicating that the group I mGluR subtypes may vary subtypes targeted for modulation by mGluRs in neocortical between cells or that these compounds were activating other receptors. The actions of (/)-a-methyl-4-carboxyphenylglycine [(/)-neurons were N-type and possibly P-type (Choi and Lov-MCPG] were consistent with it being a low-potency antagonist. inger 1996) or predominantly L-type (Sayer et al. 1992), Several features of the Ca 2/ current inhibition evoked by DHPG depending on experimental conditions. distinguished it from the rapid modulation typical of a direct action Studies of Ca 2/ channel regulation in sympathetic neurons of G proteins on Ca 2/ channels; the inhibition was slow to reach have revealed a variety of G protein-mediated mechanisms maximum (tens of seconds), current activation was not slowed or (Hille 1994). A major pathway that inhibits N-type channels shifted in the positive voltage direction, and the inhibition was not is fast, membrane delimited, does not require the presence relieved by positive prepulses. Nimodipine and v-conotoxin GVIA of Ca 2/ , and involves a shift in the voltage dependence of blocked fractions of the current and also reduced the magnitude channel gating. Another pathway is slower, probably inof the responses to DHPG, indicating that both Land N-type Ca 2/ volves a diffusible second messenger, requires Ca 2/ , is not channels were regulated. These results further differentiate the slow modulatory pathway observed in neocortical neurons when Ca 2/ associated with a gating shift, and targets Land N-type is used as the charge carrier from the rapid voltage-dependent channels. In neocortical pyramidal neurons, the mGluR-memechanism reported to inhibit Ba 2/ currents under Ca 2/-free condiated inhibition of Ba 2/ current through N-type (and possiditions.

Research paper thumbnail of On the regional distribution of muscle spindles

Behavioral and Brain Sciences, 1989

Research paper thumbnail of Motoneuron and muscle-unit properties after long-term direct innervation of soleus muscle by medial gastrocnemius nerve in cat

Journal of Neurophysiology, 1990

1. This study addresses the following questions. 1) In a previous experiment, when the combined l... more 1. This study addresses the following questions. 1) In a previous experiment, when the combined lateral gastrocnemius-soleus nerve was cross-innervated by the medial gastrocnemius (MG) nerve, was the predominance of slow muscle units in soleus muscle a result of selective routing of slow motor axons into soleus? 2) Is MG-nerve-induced conversion of soleus muscle fibers from slow to fast more complete at very long (18 mo vs. 9-11 mo) postoperative times? 3) Do MG motoneurons that cross-innervate soleus muscle recover their normal membrane electrical properties at very long postoperative times? 2. The proximal portion of approximately one-third of the MG nerve was coapted directly with the distally isolated soleus nerve. The MG muscle remained innervated by the unoperated portion of the MG nerve. At 6, 10, or 18 mos postoperative, motoneuron and/or muscle-unit properties were determined for MG motoneurons innervating MG, soleus, or neither muscle, and for axotomized soleus motoneurons...

Research paper thumbnail of Correlation of physiologically and morphologically identified neuronal types in human association cortex in vitro

Journal of Neurophysiology, 1991

1. We examined whether the three physiologically defined neuron types described for rodent neocor... more 1. We examined whether the three physiologically defined neuron types described for rodent neocortex were also evident in human association cortex studied in an in vitro brain slice preparation. We also examined the relationship between physiological and morphological cell type in human neocortical neurons. In particular, we tested whether burst-firing neurons were numerous in regions of human cortex that are susceptible to seizures. 2. Although we sampled regular-spiking and fast-spiking neurons, we observed no true burst-firing neurons, as defined for rodent cortex. We did find neurons that displayed a voltage-dependent shift in firing behavior. Because this behavior was due, in large part, to a low-threshold calcium conductance, we called these cells low-threshold spike (LTS) neurons. 3. Regular-spiking neurons and LTS neurons only differed in the voltage dependence of firing behavior and the first few interspike intervals (ISIs) of repetitive firing in response to small current ...

Research paper thumbnail of Morphological and electrophysiological properties of atypically oriented layer 2 pyramidal cells of the juvenile rat neocortex

Neuroscience, 2000

We used whole-cell patch clamp recordings combined with intracellular dye-filling to examine the ... more We used whole-cell patch clamp recordings combined with intracellular dye-filling to examine the morphological and electrophysiological properties of atypically oriented pyramidal cells located at the layer 1/2 border of the juvenile rat neocortex. Orientation of the apical dendrite varied from oblique (>20° from vertical) to truly horizontal (90° from vertical). The length of the apical dendrite ranged from 150 to

Research paper thumbnail of Essential role for phosphatidylinositol 4,5-bisphosphate in yeast cell proliferation

Research paper thumbnail of Relationship between repetitive firing and afterhyperpolarizations in human neocortical neurons

Journal of Neurophysiology, 1992

1. Human neocortical neurons fire repetitively in response to long depolarizing current injection... more 1. Human neocortical neurons fire repetitively in response to long depolarizing current injections. The slope of the relationship between average firing frequency and injected current (f-I slope) was linear or bilinear in these cells. The mean steady-state f-I slope (average of the last 500 ms of a 1-s firing episode) was 57.8 Hz/nA. The instantaneous firing rate decreased with time during a 1-s constant-current injection (spike frequency adaptation). Also, human neurons exhibited habituation in response to a 1-s current stimulus repeated every 2 s. 2. Afterhyperpolarizations (AHPs) reflect the active ionic conductances after action potentials. We studied AHPs with the use of intracellular recordings and pharmacological manipulations in the in vitro slice preparation to 1) gain insight into the ionic mechanisms underlying the AHPs and 2) elucidate the role that the underlying currents play in the functional behavior of human cortical neurons. 3. We have classified three AHPs in huma...

Research paper thumbnail of Different Ca2+ source for slow AHP in completely adapting and repetitive firing pyramidal neurons

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).

Research paper thumbnail of Morphology and histochemistry of flight muscles in free-tailed bats, Tadarida brasiliensis

Journal of mammalogy, 1984

Page 1. MORPHOLOGY AND HISTOCHEMISTRY OF FLIGHT MUSCLES IN FREE-TAILED BATS, TADARIDA BRASILIENSI... more Page 1. MORPHOLOGY AND HISTOCHEMISTRY OF FLIGHT MUSCLES IN FREE-TAILED BATS, TADARIDA BRASILIENSIS ROBERT C. FOEHRING AND JOHN W. HERMANSON Department of Neuroscience, JHMHC Box ...

Research paper thumbnail of Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro

Journal of …, 1988

SUMMARY AND CONCLUSIONS I. Potassium conductances were studied in large layer V neurons using an ... more SUMMARY AND CONCLUSIONS I. Potassium conductances were studied in large layer V neurons using an in vitro slice preparation of cat sensorimotor cortex. The kinetics and pharmacological sensitivity of K+ currents were studied directly using single microelectrode voltage clamp ...

Research paper thumbnail of Essential Role for Phosphatidylinositol 4, 5-Bisphosphate in the Expression, Regulation, and Gating of the Slow Afterhyperpolarization Current in the Cerebral Cortex

The Journal of …, 2011

Many neurons of the central and peripheral nervous system express a slow afterhyperpolarization t... more Many neurons of the central and peripheral nervous system express a slow afterhyperpolarization that is mediated by a slow calcium-activated potassium current. Previous work has shown that this aftercurrent regulates repetitive firing and is an important target for neuromodulators signaling through receptors coupled to G proteins of the Gα q-11 and Gα s subtypes. Yet, in spite of considerable effort, a molecular-level understanding of the potassium current underlying the slow afterhyperpolarization and its modulation has proven elusive. Here we use a combination of pharmacological and molecular biological approaches in cortical brain slices to show that the functional expression of the slow calcium-activated afterhyperpolarizing current in pyramidal cells is critically dependent on membrane PtdIns(4,5)P 2 and that this dependence accounts for its inhibition by 5-HT 2A receptors. Furthermore we show that PtdIns(4,5)P 2 regulates the calcium sensitivity of I sAHP in a manner that suggests it acts downstream from the rise in intracellular calcium. These results clarify key functional aspects of the slow afterhyperpolarization current and its modulation by 5-HT 2A receptors and point to a key role for PtdIns(4,5)P 2 in the gating of this current.

Research paper thumbnail of Essential Role for Phosphatidylinositol 4, 5-Bisphosphate in the Expression, Regulation, and Gating of the Slow Afterhyperpolarization Current in the Cerebral Cortex

The Journal of …, 2011

Many neurons of the central and peripheral nervous system express a slow afterhyperpolarization t... more Many neurons of the central and peripheral nervous system express a slow afterhyperpolarization that is mediated by a slow calcium-activated potassium current. Previous work has shown that this aftercurrent regulates repetitive firing and is an important target for neuromodulators signaling through receptors coupled to G proteins of the Gα q-11 and Gα s subtypes. Yet, in spite of considerable effort, a molecular-level understanding of the potassium current underlying the slow afterhyperpolarization and its modulation has proven elusive. Here we use a combination of pharmacological and molecular biological approaches in cortical brain slices to show that the functional expression of the slow calcium-activated afterhyperpolarizing current in pyramidal cells is critically dependent on membrane PtdIns(4,5)P 2 and that this dependence accounts for its inhibition by 5-HT 2A receptors. Furthermore we show that PtdIns(4,5)P 2 regulates the calcium sensitivity of I sAHP in a manner that suggests it acts downstream from the rise in intracellular calcium. These results clarify key functional aspects of the slow afterhyperpolarization current and its modulation by 5-HT 2A receptors and point to a key role for PtdIns(4,5)P 2 in the gating of this current.

Research paper thumbnail of Serotonergic Modulation of Supragranular Neurons in Rat Sensorimotor Cortex

The Journal of Neuroscience

Research paper thumbnail of Distinct Cell- and Layer-Specific Expression Patterns and Independent Regulation of Kv2 Channel Subtypes in Cortical Pyramidal Neurons

Journal of Neuroscience, 2015

Research paper thumbnail of Properties of self-reinnervated motor units of medial gastrocnemius of cat. I. Long-term reinnervation

Journal of neurophysiology, 1986

This work tested whether the membrane electrical properties of cat motoneurons, the contractile p... more This work tested whether the membrane electrical properties of cat motoneurons, the contractile properties of their muscle units, and the normal relationships among them would be restored 9 mo after section and resuture of their muscle nerve. Properties of medial gastrocnemius (MG) motor units were examined 9 mo following section and resuture of the MG nerve in adult cats. Motoneuron electrical properties and muscle-unit contractile properties were measured. Motor units were classified on the basis of their contractile properties as type fast twitch, fast fatiguing (FF), fast twitch with intermediate fatigue resistance (FI), fast twitch, fatigue resistant (FR), or slow twitch, fatigue resistant (S) (8, 20). Muscle fibers were classified as type fast glycolytic (FG), fast oxidative glycolytic (FOG), or slow oxidative (SO) on the basis of histochemical staining for myosin adenosine triphosphatase, nicotinamide adenine dinucleotide diaphorase, and alpha-glycerophosphate dehydrogenase (...

Research paper thumbnail of Norepinephrine selectively reduces slow Ca2+- and Na+-mediated K+ currents in cat neocortical neurons

Journal of neurophysiology, 1989

1. The effects of norepinephrine (NE) and related agonists and antagonists were examined on large... more 1. The effects of norepinephrine (NE) and related agonists and antagonists were examined on large neurons from layer V of cat sensorimotor cortex ("Betz cells") were examined in a brain slice preparation using intracellular recording, constant current stimulation and single microelectrode voltage clamp. 2. Application of NE (0.1-100 microM) usually caused a small depolarization from resting potential; hyperpolarizations were rare. Application of NE reversibly reduced rheobase and both the Ca2+- and Na+-dependent portions of the slow afterhyperpolarization (sAHP) that followed sustained firing evoked by constant current injection. The faster Ca2+-dependent medium afterhyperpolarization (mAHP), the fast afterhyperpolarization (fAHP), the action potential, and input resistance were unaffected. 3. The changes in excitability produced by NE application were most apparent during prolonged stimulation. The cells exhibited steady repetitive firing to currents that were formerly in...

Research paper thumbnail of alpha2-Adrenergic receptor-mediated modulation of calcium current in neocortical pyramidal neurons

Brain research, Jan 16, 2004

Noradrenergic projections to the cortex modulate a variety of cortical activities and calcium cha... more Noradrenergic projections to the cortex modulate a variety of cortical activities and calcium channels are one likely target for such modulation. We used the whole-cell patch-clamp technique to study noradrenergic modulation of barium currents in acutely dissociated pyramidal neurons from rat sensorimotor cortex. Extracellular application of specific agonists and antagonists revealed that norepinephrine (NE) reduced Ca2+ current. A major component of this modulation was due to activation of alpha2 receptors. Activation of alpha2-adrenergic receptors resulted in a fast, voltage-dependent pathway involving Gi/Go G-proteins. This pathway targeted N- and P-type calcium channels The alpha2 modulation was partially reversed by repeated action potential waveforms (APWs). N- and P-type channels have been implicated in synaptic transmission and activation of afterhyperpolarizations in these cells. Our findings suggest that NE can regulate these cellular processes by mechanisms sensitive to s...

Research paper thumbnail of Effects of spike parameters and neuromodulators on action potential waveform-induced calcium entry into pyramidal neurons

Journal of neurophysiology, 2001

Neocortical pyramidal neurons express several different calcium channel types. Previous studies w... more Neocortical pyramidal neurons express several different calcium channel types. Previous studies with square voltage steps have found modest biophysical differences between these calcium channel types as well as differences in their modulation by transmitters. We used acutely dissociated neocortical pyramidal neurons to test whether this diversity extends to different activation by physiological stimuli. We conclude that 1) peak amplitude, latency to peak, and the total charge entry for the Ca(2+) channel current is dependent on the shape of the mock action potential waveforms (APWs). 2) The percent contribution of the five high-voltage-activated currents to the whole cell current was not altered by using an APW as opposed to a voltage step to elicit the current. 3) The identity of the charge carrier affects the amplitude and decay of the whole cell current. With Ca(2+), there was a greater contribution of T-type current to the whole cell current. 4) Total Ba(2+) charge entry is line...

Research paper thumbnail of Morphological and electrophysiological properties of atypically oriented layer 2 pyramidal cells of the juvenile rat neocortex

Neuroscience, 2000

We used whole-cell patch clamp recordings combined with intracellular dye-filling to examine the ... more We used whole-cell patch clamp recordings combined with intracellular dye-filling to examine the morphological and electrophysiological properties of atypically oriented pyramidal cells located at the layer 1/2 border of the juvenile rat neocortex. Orientation of the apical dendrite varied from oblique (>20 degrees from vertical) to truly horizontal (90 degrees from vertical). The length of the apical dendrite ranged from 150 to 400 microm. The total horizontal domain of the dendritic tree (including basal dendrites) of the longest horizontal pyramids exceeded 500 microm, but we also found short horizontal cells with horizontal dendritic domains of less than 300 microm. In addition, atypically oriented pyramids had long horizontal axon collaterals in layer 1/2. Electrophysiologically, atypically oriented pyramidal cells had intrinsic membrane properties similar to regularly oriented pyramids that have been described in the superficial layers at this age in the rat. Cells that fir...

Research paper thumbnail of Dynamics in Gonadotropin-Releasing Hormone Neurons Two Slow Calcium-Activated Afterhyperpolarization Currents Control Burst Firing

(PDF) (Full Text) (Abstract)

Research paper thumbnail of Opposing Influences on cAMP Response Element-Binding Protein Estradiol Activates Group I and II Metabotropic Glutamate Receptor Signaling, Leading to

Sayer, Rod J. Group I metabotropic glutamate receptors mediate a role in autoinhibition of transm... more Sayer, Rod J. Group I metabotropic glutamate receptors mediate a role in autoinhibition of transmitter release (reviewed by slow inhibition of calcium current in neocortical neurons J. Neuro-Stefani et al. 1996b). mGluR subtypes are encoded by eight physiol. 80: 1981-1988, 1998. Metabotropic glutamate receptor known genes and are classified into three groups based on (mGluR)-mediated inhibition of high-voltage-activated Ca 2/ curamino acid sequence similarities and pharmacology: group rents was investigated in pyramidal neurons acutely isolated from I, mGluR1 and mGluR5; group II, mGluR2 and mGluR3; rat dorsal frontoparietal neocortex. Whole cell recordings were and group III, mGluR4, mGluR6, mGluR7, and mGluR8. made at 30-32ЊC, with Ca 2/ as the charge carrier. Selective ago-Splice variants have been found for several mGluR subtypes nists were used to classify the subgroup of mGluRs mediating the (for a review of mGluR classification and pharmacology see response. Ca 2/ currents were inhibited by (1S,3R)-1-aminocyclo-Conn and Pin 1997). Recent studies used selective agonists pentane-1,3-dicarboxylic acid (1S,3R-ACPD) and by the group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) but not by the to identify which groups of mGluRs are involved in Ca 2/ group II agonist (2S,2R,3R)-2-(2,3-dicarboxycyclopropyl)channel regulation. In neocortical pyramidal neurons, recepglycine (DCG-IV) or the group III agonist L (/)-2-amino-4-phostors from all three groups have been implicated; Ca 2/ chanphonobutryic acid (L-AP4). (2S,1S,2S)-2-(carboxycyclopropyl)nel inhibition was observed in response to the group I agonist glycine (L-CCG-I) was effective at 10 and 100 mM but not at 1 (RS)-3,5-dihydroxyphenylglycine (DHPG) and the group mM, consistent with involvement of group I mGluRs. Variable II agonist (2S,2R,3R)-2-(2,3-dicarboxycyclopropyl)results were obtained with the putative mGluR5-selective agonist glycine (DCG-IV) (Choi and Lovinger 1996) and also to (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) and the putative L (/)-2-amino-4-phosphonobutyric acid (L-AP4), a group mGluR1-selective antagonist (S)-4-carboxyphenylglycine [(S)-III agonist (Stefani et al. 1996a 1998). The Ca 2/ channel 4CPG], indicating that the group I mGluR subtypes may vary subtypes targeted for modulation by mGluRs in neocortical between cells or that these compounds were activating other receptors. The actions of (/)-a-methyl-4-carboxyphenylglycine [(/)-neurons were N-type and possibly P-type (Choi and Lov-MCPG] were consistent with it being a low-potency antagonist. inger 1996) or predominantly L-type (Sayer et al. 1992), Several features of the Ca 2/ current inhibition evoked by DHPG depending on experimental conditions. distinguished it from the rapid modulation typical of a direct action Studies of Ca 2/ channel regulation in sympathetic neurons of G proteins on Ca 2/ channels; the inhibition was slow to reach have revealed a variety of G protein-mediated mechanisms maximum (tens of seconds), current activation was not slowed or (Hille 1994). A major pathway that inhibits N-type channels shifted in the positive voltage direction, and the inhibition was not is fast, membrane delimited, does not require the presence relieved by positive prepulses. Nimodipine and v-conotoxin GVIA of Ca 2/ , and involves a shift in the voltage dependence of blocked fractions of the current and also reduced the magnitude channel gating. Another pathway is slower, probably inof the responses to DHPG, indicating that both Land N-type Ca 2/ volves a diffusible second messenger, requires Ca 2/ , is not channels were regulated. These results further differentiate the slow modulatory pathway observed in neocortical neurons when Ca 2/ associated with a gating shift, and targets Land N-type is used as the charge carrier from the rapid voltage-dependent channels. In neocortical pyramidal neurons, the mGluR-memechanism reported to inhibit Ba 2/ currents under Ca 2/-free condiated inhibition of Ba 2/ current through N-type (and possiditions.

Research paper thumbnail of On the regional distribution of muscle spindles

Behavioral and Brain Sciences, 1989

Research paper thumbnail of Motoneuron and muscle-unit properties after long-term direct innervation of soleus muscle by medial gastrocnemius nerve in cat

Journal of Neurophysiology, 1990

1. This study addresses the following questions. 1) In a previous experiment, when the combined l... more 1. This study addresses the following questions. 1) In a previous experiment, when the combined lateral gastrocnemius-soleus nerve was cross-innervated by the medial gastrocnemius (MG) nerve, was the predominance of slow muscle units in soleus muscle a result of selective routing of slow motor axons into soleus? 2) Is MG-nerve-induced conversion of soleus muscle fibers from slow to fast more complete at very long (18 mo vs. 9-11 mo) postoperative times? 3) Do MG motoneurons that cross-innervate soleus muscle recover their normal membrane electrical properties at very long postoperative times? 2. The proximal portion of approximately one-third of the MG nerve was coapted directly with the distally isolated soleus nerve. The MG muscle remained innervated by the unoperated portion of the MG nerve. At 6, 10, or 18 mos postoperative, motoneuron and/or muscle-unit properties were determined for MG motoneurons innervating MG, soleus, or neither muscle, and for axotomized soleus motoneurons...

Research paper thumbnail of Correlation of physiologically and morphologically identified neuronal types in human association cortex in vitro

Journal of Neurophysiology, 1991

1. We examined whether the three physiologically defined neuron types described for rodent neocor... more 1. We examined whether the three physiologically defined neuron types described for rodent neocortex were also evident in human association cortex studied in an in vitro brain slice preparation. We also examined the relationship between physiological and morphological cell type in human neocortical neurons. In particular, we tested whether burst-firing neurons were numerous in regions of human cortex that are susceptible to seizures. 2. Although we sampled regular-spiking and fast-spiking neurons, we observed no true burst-firing neurons, as defined for rodent cortex. We did find neurons that displayed a voltage-dependent shift in firing behavior. Because this behavior was due, in large part, to a low-threshold calcium conductance, we called these cells low-threshold spike (LTS) neurons. 3. Regular-spiking neurons and LTS neurons only differed in the voltage dependence of firing behavior and the first few interspike intervals (ISIs) of repetitive firing in response to small current ...

Research paper thumbnail of Morphological and electrophysiological properties of atypically oriented layer 2 pyramidal cells of the juvenile rat neocortex

Neuroscience, 2000

We used whole-cell patch clamp recordings combined with intracellular dye-filling to examine the ... more We used whole-cell patch clamp recordings combined with intracellular dye-filling to examine the morphological and electrophysiological properties of atypically oriented pyramidal cells located at the layer 1/2 border of the juvenile rat neocortex. Orientation of the apical dendrite varied from oblique (>20° from vertical) to truly horizontal (90° from vertical). The length of the apical dendrite ranged from 150 to

Research paper thumbnail of Essential role for phosphatidylinositol 4,5-bisphosphate in yeast cell proliferation

Research paper thumbnail of Relationship between repetitive firing and afterhyperpolarizations in human neocortical neurons

Journal of Neurophysiology, 1992

1. Human neocortical neurons fire repetitively in response to long depolarizing current injection... more 1. Human neocortical neurons fire repetitively in response to long depolarizing current injections. The slope of the relationship between average firing frequency and injected current (f-I slope) was linear or bilinear in these cells. The mean steady-state f-I slope (average of the last 500 ms of a 1-s firing episode) was 57.8 Hz/nA. The instantaneous firing rate decreased with time during a 1-s constant-current injection (spike frequency adaptation). Also, human neurons exhibited habituation in response to a 1-s current stimulus repeated every 2 s. 2. Afterhyperpolarizations (AHPs) reflect the active ionic conductances after action potentials. We studied AHPs with the use of intracellular recordings and pharmacological manipulations in the in vitro slice preparation to 1) gain insight into the ionic mechanisms underlying the AHPs and 2) elucidate the role that the underlying currents play in the functional behavior of human cortical neurons. 3. We have classified three AHPs in huma...

Research paper thumbnail of Different Ca2+ source for slow AHP in completely adapting and repetitive firing pyramidal neurons

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).

Research paper thumbnail of Morphology and histochemistry of flight muscles in free-tailed bats, Tadarida brasiliensis

Journal of mammalogy, 1984

Page 1. MORPHOLOGY AND HISTOCHEMISTRY OF FLIGHT MUSCLES IN FREE-TAILED BATS, TADARIDA BRASILIENSI... more Page 1. MORPHOLOGY AND HISTOCHEMISTRY OF FLIGHT MUSCLES IN FREE-TAILED BATS, TADARIDA BRASILIENSIS ROBERT C. FOEHRING AND JOHN W. HERMANSON Department of Neuroscience, JHMHC Box ...

Research paper thumbnail of Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro

Journal of …, 1988

SUMMARY AND CONCLUSIONS I. Potassium conductances were studied in large layer V neurons using an ... more SUMMARY AND CONCLUSIONS I. Potassium conductances were studied in large layer V neurons using an in vitro slice preparation of cat sensorimotor cortex. The kinetics and pharmacological sensitivity of K+ currents were studied directly using single microelectrode voltage clamp ...

Research paper thumbnail of Essential Role for Phosphatidylinositol 4, 5-Bisphosphate in the Expression, Regulation, and Gating of the Slow Afterhyperpolarization Current in the Cerebral Cortex

The Journal of …, 2011

Many neurons of the central and peripheral nervous system express a slow afterhyperpolarization t... more Many neurons of the central and peripheral nervous system express a slow afterhyperpolarization that is mediated by a slow calcium-activated potassium current. Previous work has shown that this aftercurrent regulates repetitive firing and is an important target for neuromodulators signaling through receptors coupled to G proteins of the Gα q-11 and Gα s subtypes. Yet, in spite of considerable effort, a molecular-level understanding of the potassium current underlying the slow afterhyperpolarization and its modulation has proven elusive. Here we use a combination of pharmacological and molecular biological approaches in cortical brain slices to show that the functional expression of the slow calcium-activated afterhyperpolarizing current in pyramidal cells is critically dependent on membrane PtdIns(4,5)P 2 and that this dependence accounts for its inhibition by 5-HT 2A receptors. Furthermore we show that PtdIns(4,5)P 2 regulates the calcium sensitivity of I sAHP in a manner that suggests it acts downstream from the rise in intracellular calcium. These results clarify key functional aspects of the slow afterhyperpolarization current and its modulation by 5-HT 2A receptors and point to a key role for PtdIns(4,5)P 2 in the gating of this current.

Research paper thumbnail of Essential Role for Phosphatidylinositol 4, 5-Bisphosphate in the Expression, Regulation, and Gating of the Slow Afterhyperpolarization Current in the Cerebral Cortex

The Journal of …, 2011

Many neurons of the central and peripheral nervous system express a slow afterhyperpolarization t... more Many neurons of the central and peripheral nervous system express a slow afterhyperpolarization that is mediated by a slow calcium-activated potassium current. Previous work has shown that this aftercurrent regulates repetitive firing and is an important target for neuromodulators signaling through receptors coupled to G proteins of the Gα q-11 and Gα s subtypes. Yet, in spite of considerable effort, a molecular-level understanding of the potassium current underlying the slow afterhyperpolarization and its modulation has proven elusive. Here we use a combination of pharmacological and molecular biological approaches in cortical brain slices to show that the functional expression of the slow calcium-activated afterhyperpolarizing current in pyramidal cells is critically dependent on membrane PtdIns(4,5)P 2 and that this dependence accounts for its inhibition by 5-HT 2A receptors. Furthermore we show that PtdIns(4,5)P 2 regulates the calcium sensitivity of I sAHP in a manner that suggests it acts downstream from the rise in intracellular calcium. These results clarify key functional aspects of the slow afterhyperpolarization current and its modulation by 5-HT 2A receptors and point to a key role for PtdIns(4,5)P 2 in the gating of this current.

Research paper thumbnail of Serotonergic Modulation of Supragranular Neurons in Rat Sensorimotor Cortex

The Journal of Neuroscience

Research paper thumbnail of Distinct Cell- and Layer-Specific Expression Patterns and Independent Regulation of Kv2 Channel Subtypes in Cortical Pyramidal Neurons

Journal of Neuroscience, 2015

Research paper thumbnail of Properties of self-reinnervated motor units of medial gastrocnemius of cat. I. Long-term reinnervation

Journal of neurophysiology, 1986

This work tested whether the membrane electrical properties of cat motoneurons, the contractile p... more This work tested whether the membrane electrical properties of cat motoneurons, the contractile properties of their muscle units, and the normal relationships among them would be restored 9 mo after section and resuture of their muscle nerve. Properties of medial gastrocnemius (MG) motor units were examined 9 mo following section and resuture of the MG nerve in adult cats. Motoneuron electrical properties and muscle-unit contractile properties were measured. Motor units were classified on the basis of their contractile properties as type fast twitch, fast fatiguing (FF), fast twitch with intermediate fatigue resistance (FI), fast twitch, fatigue resistant (FR), or slow twitch, fatigue resistant (S) (8, 20). Muscle fibers were classified as type fast glycolytic (FG), fast oxidative glycolytic (FOG), or slow oxidative (SO) on the basis of histochemical staining for myosin adenosine triphosphatase, nicotinamide adenine dinucleotide diaphorase, and alpha-glycerophosphate dehydrogenase (...

Research paper thumbnail of Norepinephrine selectively reduces slow Ca2+- and Na+-mediated K+ currents in cat neocortical neurons

Journal of neurophysiology, 1989

1. The effects of norepinephrine (NE) and related agonists and antagonists were examined on large... more 1. The effects of norepinephrine (NE) and related agonists and antagonists were examined on large neurons from layer V of cat sensorimotor cortex ("Betz cells") were examined in a brain slice preparation using intracellular recording, constant current stimulation and single microelectrode voltage clamp. 2. Application of NE (0.1-100 microM) usually caused a small depolarization from resting potential; hyperpolarizations were rare. Application of NE reversibly reduced rheobase and both the Ca2+- and Na+-dependent portions of the slow afterhyperpolarization (sAHP) that followed sustained firing evoked by constant current injection. The faster Ca2+-dependent medium afterhyperpolarization (mAHP), the fast afterhyperpolarization (fAHP), the action potential, and input resistance were unaffected. 3. The changes in excitability produced by NE application were most apparent during prolonged stimulation. The cells exhibited steady repetitive firing to currents that were formerly in...

Research paper thumbnail of alpha2-Adrenergic receptor-mediated modulation of calcium current in neocortical pyramidal neurons

Brain research, Jan 16, 2004

Noradrenergic projections to the cortex modulate a variety of cortical activities and calcium cha... more Noradrenergic projections to the cortex modulate a variety of cortical activities and calcium channels are one likely target for such modulation. We used the whole-cell patch-clamp technique to study noradrenergic modulation of barium currents in acutely dissociated pyramidal neurons from rat sensorimotor cortex. Extracellular application of specific agonists and antagonists revealed that norepinephrine (NE) reduced Ca2+ current. A major component of this modulation was due to activation of alpha2 receptors. Activation of alpha2-adrenergic receptors resulted in a fast, voltage-dependent pathway involving Gi/Go G-proteins. This pathway targeted N- and P-type calcium channels The alpha2 modulation was partially reversed by repeated action potential waveforms (APWs). N- and P-type channels have been implicated in synaptic transmission and activation of afterhyperpolarizations in these cells. Our findings suggest that NE can regulate these cellular processes by mechanisms sensitive to s...

Research paper thumbnail of Effects of spike parameters and neuromodulators on action potential waveform-induced calcium entry into pyramidal neurons

Journal of neurophysiology, 2001

Neocortical pyramidal neurons express several different calcium channel types. Previous studies w... more Neocortical pyramidal neurons express several different calcium channel types. Previous studies with square voltage steps have found modest biophysical differences between these calcium channel types as well as differences in their modulation by transmitters. We used acutely dissociated neocortical pyramidal neurons to test whether this diversity extends to different activation by physiological stimuli. We conclude that 1) peak amplitude, latency to peak, and the total charge entry for the Ca(2+) channel current is dependent on the shape of the mock action potential waveforms (APWs). 2) The percent contribution of the five high-voltage-activated currents to the whole cell current was not altered by using an APW as opposed to a voltage step to elicit the current. 3) The identity of the charge carrier affects the amplitude and decay of the whole cell current. With Ca(2+), there was a greater contribution of T-type current to the whole cell current. 4) Total Ba(2+) charge entry is line...

Research paper thumbnail of Morphological and electrophysiological properties of atypically oriented layer 2 pyramidal cells of the juvenile rat neocortex

Neuroscience, 2000

We used whole-cell patch clamp recordings combined with intracellular dye-filling to examine the ... more We used whole-cell patch clamp recordings combined with intracellular dye-filling to examine the morphological and electrophysiological properties of atypically oriented pyramidal cells located at the layer 1/2 border of the juvenile rat neocortex. Orientation of the apical dendrite varied from oblique (>20 degrees from vertical) to truly horizontal (90 degrees from vertical). The length of the apical dendrite ranged from 150 to 400 microm. The total horizontal domain of the dendritic tree (including basal dendrites) of the longest horizontal pyramids exceeded 500 microm, but we also found short horizontal cells with horizontal dendritic domains of less than 300 microm. In addition, atypically oriented pyramids had long horizontal axon collaterals in layer 1/2. Electrophysiologically, atypically oriented pyramidal cells had intrinsic membrane properties similar to regularly oriented pyramids that have been described in the superficial layers at this age in the rat. Cells that fir...