Luciana Izquierdo | Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) (original) (raw)

Papers by Luciana Izquierdo

Neurobiology of Learning and Memory, 2014

We investigate whether the extinction of inhibitory avoidance (IA) learning can be subjected to e... more We investigate whether the extinction of inhibitory avoidance (IA) learning can be subjected to endogenous state-dependence with systemic injections of epinephrine (E), and whether endogenous norepinephrine (NE) and the nucleus tractus solitarius (NTS) ? locus coeruleus ? hippocampus/amygdala (HIPP/BLA) pathway participate in this. Rats trained in IA were submitted to two sessions of extinction 24 h apart: In the first, the animals were submitted to a training session of extinction, and in the second they were tested for the retention of extinction. Saline or E were given i.p. immediately after the extinction training (post-extinction training injections) and/or 6 min before the extinction test (pre-extinction test). Post-extinction training E (50 or 100 lg/kg) induced a poor retrieval of extinction in the test session of this task unless an additional E injection (50 lg/kg) was given prior to the extinction test. This suggested state-dependence. Muscimol (0.01 lg/side) microinfused into the NTS prior to the extinction test session blocked E-induced state-dependence. Norepinephrine (NE, 1 lg/side) infused bilaterally into NTS restores the extinction impairment caused by post-extinction training i.p. E. In animals with bilateral NTS blockade induced by muscimol, NE (1 lg/side) given prior to the extinction test into the CA1 region of the dorsal hippocampus or into the basolateral amygdala restored the normal extinction levels that had been impaired by muscimol. These results suggest a role for the NTS ? locus coeruleus ? HIPP/BLA pathway in the retrieval of extinction, as it has been shown to have in the consolidation of inhibitory avoidance and of object recognition learning.

Proceedings of the National Academy of Sciences, 2012

Extinction of contextual fear in rats is enhanced by exposure to a novel environment at 1–2 h bef... more Extinction of contextual fear in rats is enhanced by exposure to a novel environment at 1–2 h before or 1 h after extinction training. This effect is antagonized by administration of protein synthesis inhibitors anisomycin and rapamycin into the hippocampus, but not into the amygdala, immediately after either novelty or extinction training, as well as by the gene expression blocker 5,6-dichloro-1-beta- D -ribofuranosylbenzimidazole administered after novelty training, but not after extinction training. Thus, this effect can be attributed to a mechanism similar to synaptic tagging, through which long-term potentiation can be enhanced by other long-term potentiations or by exposure to a novel environment in a protein synthesis-dependent fashion. Extinction learning produces a tag at the appropriate synapses, whereas novelty learning causes the synthesis of plasticity-related proteins that are captured by the tag, strengthening the synapses that generated this tag.

Author contributions: J.d.C.M. and I.I. designed research; J.d.C.M. and F.B. performed research; ... more Author contributions: J.d.C.M. and I.I. designed research; J.d.C.M. and F.B. performed research; J.d.C.M. analyzed data; and J.d.C.M. and I.I. wrote the paper.

Behavioural Brain Research, 2012

The multiple memory systems theory proposes that the hippocampus and the dorsolateral striatum ar... more The multiple memory systems theory proposes that the hippocampus and the dorsolateral striatum are the core structures of the spatial/relational and stimulus-response (S-R) memory systems, respectively. This theory is supported by double dissociation studies showing that the spatial and cue (S-R) versions of the Morris water maze are impaired by lesions in the dorsal hippocampus and dorsal striatum, respectively. In the present study we further investigated whether adult male Wistar rats bearing double and bilateral electrolytic lesions in the dorsal hippocampus and dorsolateral striatum were as impaired as rats bearing single lesions in just one of these structures in learning both versions of the water maze. Such a prediction, based on the multiple memory systems theory, was not confirmed. Compared to the controls, the animals with double lesions exhibited no improvement at all in the spatial version and learned the cued version very slowly. These results suggest that, instead of independent systems competing for holding control over navigational behaviour, the hippocampus and dorsal striatum both play critical roles in navigation based on spatial or cue-based strategies.

The British Journal of Psychiatry, 2008

Behavioural Brain Research, 1982

The intracerebroventricular (icv) administration of 5.0 or 25.0 ng of beta-endorphin or Met-enkep... more The intracerebroventricular (icv) administration of 5.0 or 25.0 ng of beta-endorphin or Met-enkephalin causes retrograde amnesia for a shuttle avoidance task ion rats. In both cases, the higher dose was more effective than the lower one. The present results confirm previous similar findings obtained using systemic administrations of these compounds, and suggest that the amnestic effect of beta-endorphin and Met-enkephalin is mediated centrally.

Neurobiology of learning and memory, 2007

Ki values between 10 and 50 nM in different brain regions.The GABA ratio of 1.03 for [ 3 H]flunit... more Ki values between 10 and 50 nM in different brain regions.The GABA ratio of 1.03 for [ 3 H]flunitrazepam binding to cerebral cortex, 0.76 for cerebellum, 0.7 for hippocampus, 0.7 for striatum, and 0.8 for spinal cord indicated an antagonistic or weak inverse agonistic profile of 6-methyl-3-bromoflavone on BDZ-bs. Unlike classical benzodiazepines, it had no anticonvulsant, anxiolytic, myorelaxant, sedative, amnestic or motor incoordination effects. However, it antagonized the muscle relaxant, the sedative effect, and the changes in locomotor activity induced by diazepam. Taken together, these findings suggest that 6-methyl-3-bromoflavone has an antagonistic profile on the BDZ-bs.

Neurobiology of Learning and Memory, 2006

In this study, we analyzed the participation of the entorhinal cortex in extinction of a learned ... more In this study, we analyzed the participation of the entorhinal cortex in extinction of a learned aversive response. Rats with infusion cannulae aimed to the entorhinal cortex were trained in a one-trial step-down inhibitory avoidance task (IA) and submitted to four consecutive daily test sessions without the footshock, a procedure that induced extinction of the conditioned response in control animals.

Current Drug Targets - Cns & Neurological Disorders, 2003

Recent pharmacological findings have shown that retrieval of one-trial avoidance learning require... more Recent pharmacological findings have shown that retrieval of one-trial avoidance learning requires glutamate receptors, cAMP-dependent protein kinase and mitogen-activated protein kinases in the hippocampus, entorhinal, posterior parietal and anterior cingulate cortex. It requires AMPA but not other type of glutamate receptors or the protein kinases in the amygdala. Retrieval is modulated by dopamine D1, beta-noradrenergic, serotonin 1A and cholinergic receptors in the four cortical structures mentioned, and by beta-noradrenergic receptors in the basolateral amygdala. Further, retrieval is also modulated by peripheral ACTH, glucocorticoids, vasopressin, beta-endorphin and catecholamines; these hormones probably act through beta-noradrenergic receptor systems in the basolateral amygdala. Exposure to novelty or the systemic administration of antidepressant drugs prior to retention tests enhances retrieval, even for very remote memories. The effect of novelty is mediated by molecular mechanisms similar to those of retrieval itself.

Cellular and molecular neurobiology, 2002

1. It has been discussed for over 100 years whether short-term memory (STM) is separate from, or ... more 1. It has been discussed for over 100 years whether short-term memory (STM) is separate from, or just an early phase of, long-term memory (LTM). The only way to solve this dilemma is to find out at least one treatment that blocks STM while keeping LTM intact for the same task in the same animal. 2. The effect of a large number of treatments infused into the hippocampus, amygdala, and entorhinal, posterior parietal or prefrontal cortex on STM and LTM of a one-trial step-down inhibitory avoidance task was studied. The animals were tested at 1.5 h for STM, and again at 24 h for LTM. The treatments were given after training. 3. Eleven different treatments blocked STM without affecting LTM. Eighteen treatments affected the two memory types differentially, either blocking or enhancing LTM alone. Thus, STM is separate from, and parallel to the first hours of processing of, LTM of that task. 4. The mechanisms of STM are different from those of LTM. The former do not include gene expression ...

Neurobiology of Learning and Memory, 2000

Rats were implanted with cannulae in the CA1 area of the dorsal hippocampus or in the entorhinal ... more Rats were implanted with cannulae in the CA1 area of the dorsal hippocampus or in the entorhinal cortex and trained in one-trial step-down inhibitory avoidance. Two retention tests were carried out in each animal, one at 1.5 h to measure shortterm memory (STM) and another at 24 h to measure long-term memory (LTM). The purpose of the present study was to screen the effect on STM of various drugs previously shown to affect LTM of this task when given posttraining at the same doses that were used here. The drugs and doses were the guanylyl cyclase inhibitor LY83583 (LY, 2.5 g), the inhibitor of Tyr-protein kinase at low concentrations and of protein kinase G (PKG) at higher concentrations lavendustin A (LAV, 0.1 and 0.5 g), the PKG inhibitor KT5823 (2.0 g), the protein kinase C (PKC) inhibitor staurosporin (STAU, 2.5 g), the inhibitor of calcium/ calmodulin protein kinase II (CaMKII) KN62 (3.6 g), the protein kinase A (PKA) inhibitor KT5720 (0.5 g), and the mitogen-activated protein kinase kinase (MAPKK) inhibitor PD098059 (PD, 0.05 g). PD was dissolved in saline; all the other drugs were dissolved in 20% dimethyl sulfoxide. In all cases the drugs affected LTM as had been described in previous papers. The drugs affected STM and LTM differentially depending on the brain structure into which they were infused. STM was inhibited by KT5720, LY, and PD given into CA1 and by STAU and KT5720 given into the entorhinal cortex. PD given into the entorhinal cortex enhanced STM. LTM was inhibited by STAU, KN62, KT5720, KT5823, and LAV (0.5 g) given into CA1 and by STAU, KT5720, and PD given into the entorhinal cortex. The results suggest that STM and LTM involve different physiological mechanisms but are to an extent linked. STM appears to require PKA, guanylyl cyclase, and MAPKK activity in CA1 and PKA and PKC activity in the entorhinal cortex; MAPKK seems to play an inhibitory role in STM in the entorhinal cortex. In contrast, LTM appears to

Neurochemical Research, 2002

Memory retrieval is a fundamental component or stage of memory processing. In fact, retrieval is ... more Memory retrieval is a fundamental component or stage of memory processing. In fact, retrieval is the only possible measure of memory. The ability to recall past events is a major determinant of survival strategies in all species and is of paramount importance in determining our uniqueness as individuals. Most biological studies of memory using brain lesion and/or gene manipulation techniques cannot distinguish between effects on the molecular mechanisms of the encoding or consolidation of memories and those responsible for their retrieval from storage. Here we examine recent findings indicating the major molecular steps involved in memory retrieval in selected brain regions of the mammalian brain. Together the findings strongly suggest that memory formation and retrieval may share some molecular mechanisms in the hippocampus and that retrieval initiates extinction requiring activation of several signaling cascades and protein synthesis.

Peptides, 1999

The purpose of the present study was to evaluate the possible effect of melanin-concentrating hor... more The purpose of the present study was to evaluate the possible effect of melanin-concentrating hormone (MCH) on learning and memory by using the one-trial step-down inhibitory avoidance test in rats. The peptide was infused into hippocampus, amygdala, and entorhinal cortex. MCH caused retrograde facilitation when given at 0 or 4 h post-training into hippocampus, but only at 0 h into

Brazilian Journal of Medical and Biological Research, 2001

Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or the entor... more Rats implanted bilaterally with cannulae in the CA1 region of the dorsal hippocampus or the entorhinal cortex were submitted to either a one-trial inhibitory avoidance task, or to 5 min of habituation to an open field. Immediately after training, they received intrahippocampal or intraentorhinal 0.5-µl infusions of saline, of a vehicle (2% dimethylsulfoxide in saline), of the glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphono pentanoic acid (AP5), of the protein kinase A inhibitor Rp-cAMPs (0.5 µg/side), of the calcium-calmodulin protein kinase II inhibitor KN-62, of the dopaminergic D 1 antagonist SCH23390, or of the mitogen-activated protein kinase kinase inhibitor PD098059. Animals were tested in each task 24 h after training. Intrahippocampal KN-62 was amnestic for habituation; none of the other treatments had any effect on the retention of this task. In contrast, all of them strongly affected memory of the avoidance task. Intrahippocampal Rp-cAMPs, KN-62 and AP5, and intraentorhinal Rp-cAMPs, KN-62, PD098059 and SCH23390 caused retrograde amnesia. In view of the known actions of the treatments used, the present findings point to important biochemical differences in memory consolidation processes of the two tasks. Research supported by a travel grant from Agencia para el Desarrollo Científico y Tecnológico (Argentina), FAPERGS and PRONEX. L.A. Izquierdo, D.M. Barros and M.M. de Souza are recipients of CAPES fellowships, and M.R.M.

Neurotoxicity Research, 2002

Many, if not all psychiatric diseases are accompanied by memory disturbances, in particular, the ... more Many, if not all psychiatric diseases are accompanied by memory disturbances, in particular, the dementias, schizophrenia, and, to an extent, mood disorders. Anxiety and stress, on the other hand, cause important alterations of memory, particularly its retrieval. Here we discuss several new findings on the basic mechanisms of consolidation, retrieval and extinction of a prototype form of episodic memory in the rat: conditioned fear. The findings point the way for investigations on the pathology of these aspects of memory in health and disease. Emphasis is placed on the parallel processing Of retrieval in several cortical areas, on the links between retrieval and the onset of extinction, on the fact that extinction involves new learning requiring gene expression, and on the differences between the retrieval of recent or remote long-term memories.

Neurobiology of Learning and Memory, 1997

Retrograde amnesia was induced in rats trained in step-down inhibitory avoidance by four differen... more Retrograde amnesia was induced in rats trained in step-down inhibitory avoidance by four different treatments: an ip injection of b-endorphin (1.0 mg kg), an electroconvulsive shock (ECS), an intrahippocampal infusion of the calcium/calmodulin protein kinase II inhibitor, KN62 (0.08 mg/side), given 0 h after training, or an intrahippocampal infusion of the protein kinase A inhibitor, KT5720 (0.5 mg/side), given 3 h after training. Pretest ip injections of ACTH (0.2 mg/kg) or vasopressin (10.0 mg/kg), but not saline, reversed the amnesia caused by b-endorphin and ECS but not that caused by the enzyme inhibitors. This suggests that the amnesia produced by intrahippocampal KN62 and KT5720 administration is stronger than that caused by ECS and b-endorphin, possibly because the former interfere directly with specific steps of the core biochemical chain of events that underlies memory consolidation. ᭧ 1997 Academic Press

Neurobiology of Learning and Memory, 2007

The dorsolateral and medial prefrontal cortex are critical for immediate memory processing. The p... more The dorsolateral and medial prefrontal cortex are critical for immediate memory processing. The possibility has been raised that those two areas may also contribute to long-term memory formation. Here, we studied the role of specific receptors in dorsolateral and medial prefrontal cortex in immediate and in long-term memory formation of one-trial inhibitory avoidance. Four different specific receptor ligands were infused into these two areas: the dopamine D1 receptor antagonist, SCH23390, the GABA(A) receptor agonist, muscimol, the AMPA glutamatergic receptor antagonist, ciano-nitro-quinoxaline-dione (CNQX), and the NMDA glutamatergic receptor antagonist, aminophosphonovaleric acid (AP5). In all cases the doses used had been previously shown to affect immediate or long-term memory. In the experiments on immediate memory the drugs were given 5 min before training and the animals were tested 3s post-training. These animals were then also tested 24h later for long-term memory. The effect of the treatments on long-term memory was studied by their infusion 0, 90, 180 or 270 min post-training, testing the animals 24h after training. Immediate memory was inhibited by SCH23390, muscimol and CNQX, but not by AP5, given into any of the two subregions. Long-term memory formation was inhibited by SCH23390, muscimol and CNQX, but not by AP5, given pre-training or 0, 90 or 180 but not 270 min post-training into the dorsolateral region; or 90 but not 0 or 180 min post-training into the medial region. Thus, there is a time- and receptor-dependent correlation in the two areas between their role in immediate and in long-term memory processing. Both roles require intact glutamate AMPA and dopamine D1 receptors, are inhibited by GABAergic synapses, and are unaffected by AP5. In the dorsolateral prefrontal cortex the link between immediate and long-term memory appears to be direct; in the medial area the link suffers a 90 min delay.

Neurobiology of Learning and Memory, 1998

Rats with cannulae implanted in the dorsal CA1 region of the hippocampus or in the entorhinal cor... more Rats with cannulae implanted in the dorsal CA1 region of the hippocampus or in the entorhinal cortex (EC) were trained in one-trial step-down inhibitory avoidance and tested 1.5 or 24 h later, in order to measure short-term memory (STM) and longterm memory (LTM) respectively. Several drugs infused immediately post-training inhibited STM without altering LTM: the D1 receptor agonist SKF38393 (7.5 mg) given into either CA1 or EC, the b blocker timolol (0.3 mg) given into EC, the 5HT1A receptor agonist 8-HO-DPAT (2.5 mg) given into CA1, and the 5HT1A antagonist NAN-190 (2.5 mg) given into EC. These findings indicate that STM is not a necessary step toward LTM. Intraentorhinal 8-HO-DPAT enhanced STM and depressed LTM. The D1 antagonist SCH23390 (0.5 mg) enhanced STM without affecting LTM when given into CA1, and blocked LTM without affecting STM when given into EC. Intraentorhinal norepinephrine (0.3 mg) enhanced both STM and LTM, and the same drug when given into CA1 enhanced LTM selectively. None of the drugs had any effect on retrieval of either STM or LTM when given prior to testing. The data indicate that STM and LTM are differentially modulated by D1, b, and 5HT1A receptors in CA1 and EC. ᭧ 1998 Academic Press Long-term memory (LTM) becomes fully consolidated only several hours after acquisition . This involves interactions between the CA1 area of the hippocampus and the entorhinal cortex (EC) (Izquierdo,