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1.
Proc Natl Acad Sci U S A ; 119(49): e2208254119, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36442129

RESUMEN

Detecting novelty is critical to consolidate declarative memories, such as spatial contextual recognition memory. It has been shown that stored memories, when retrieved, are susceptible to modification, incorporating new information through an updating process. Catecholamine release in the hippocampal CA1 region consolidates an object location memory (OLM). This work hypothesized that spatial contextual memory updating could be changed by decreasing catecholamine release in the hippocampal CA1 terminals from the locus coeruleus (LC). In a mouse model expressing Cre-recombinase under the control of the tyrosine hydroxylase (TH) promoter, memory updating was impaired by photoinhibition of the CA1 catecholaminergic terminals from the LC (LC-CA1) but not from the ventral tegmental area (VTA-CA1). In vivo microdialysis confirmed that the extracellular concentration of both dopamine (DA) and noradrenaline (NA) decreased after photoinhibition of the LC-CA1 terminals (but not VTA-CA1) during the OLM update session. Furthermore, DA D1/D5 and beta-adrenergic receptor antagonists disrupted behavior, but only the former impaired memory updating. Finally, photoinhibition of LC-CA1 terminals suppressed long-term potentiation (LTP) induction in Schaffer's collaterals as a plausible mechanism for memory updating. These data will help understand the underpinning mechanisms of DA in spatial contextual memory updating.


Asunto(s)
Dopamina , Locus Coeruleus , Animales , Ratones , Memoria Espacial , Hipocampo , Catecolaminas
2.
Neurobiol Learn Mem ; 205: 107840, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37805119

RESUMEN

Environmental enrichment (EE) is known to improve memory and cognition and modulate the impact of aversive stimuli in animals, promoting the development of resilience to stressful situations. Likewise, it is known that EE can modulate synaptic plasticity as is the case of long-term potentiation (LTP). These findings have been described initially in ex vivo preparations, suggesting that the effects of EE are the result of an early modification of the synaptic excitability and transmission. In this regard, it is known that metaplasticity refers to the persistent modification, by previous activity, in the ability to induce synaptic plasticity. Our previous studies have shown that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) in vivo. In addition, we have shown that CTA extinction allows the induction but not the maintenance of IC-LTP of the Bla-IC pathway. Recently, we also showed that prior exposure to environmental enrichment for three weeks reduces the strength of CTA, restoring the brain-derived neurotrophic factor (BDNF) levels in the IC. The present study aimed to analyze the effects of brief exposure to an enriched environment on the strength of aversive memory, as well as on the in vivo IC-LTP. To do so, adult rats were exposed for seven days to an EE, either before CTA training or LTP induction in the Bla-IC pathway. Our results demonstrate that a seven-day exposure to an enriched environment attenuates the aversive response to a strong CTA and allows the induction but not the maintenance of LTP in the insular cortex. These findings provide evidence that metaplastic regulation in a neocortical region takes part in the mechanisms through which brief exposure to enriched environments attenuates an aversive response.


Asunto(s)
Corteza Insular , Gusto , Animales , Ratas , Reacción de Prevención/fisiología , Corteza Cerebral/fisiología , Condicionamiento Clásico/fisiología , Plasticidad Neuronal , Gusto/fisiología
3.
Neurobiol Learn Mem ; 205: 107845, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37865264

RESUMEN

The presentation of novel stimuli induces a reliable dopamine release in the insular cortex (IC) from the ventral tegmental area (VTA). The novel stimuli could be associated with motivational and emotional signals induced by cortical glutamate release from the basolateral amygdala (BLA). Dopamine and glutamate are essential for acquiring and maintaining behavioral tasks, including visual and taste recognition memories. In this study, we hypothesize that the simultaneous activation of dopaminergic and glutamatergic projections to the neocortex can underlie synaptic plasticity. High-frequency stimulation of the BLA-IC circuit has demonstrated a reliable long-term potentiation (LTP), a widely acknowledged synaptic plasticity that underlies memory consolidation. Therefore, the concurrent optogenetic stimulation of the insula's glutamatergic and dopaminergic terminal fibers would induce reliable LTP. Our results confirmed that combined photostimulation of the VTA and BLA projections to the IC induces a slow-onset LTP. We also found that optogenetically-induced LTP in the IC relies on both glutamatergic NMDA receptors and dopaminergic D1/D5 receptors, suggesting that the combined effects of these neurotransmitters can trigger synaptic plasticity in the neocortex. Overall, our findings provide compelling evidence supporting the essential role of both dopaminergic and glutamatergic projections in modulating synaptic plasticity within the IC. Furthermore, our results suggest that the synergistic actions of these projections have a pivotal influence on the formation of motivational memories.


Asunto(s)
Complejo Nuclear Basolateral , Potenciación a Largo Plazo , Ratas , Animales , Potenciación a Largo Plazo/fisiología , Área Tegmental Ventral/fisiología , Corteza Insular , Ratas Wistar , Dopamina/farmacología , Glutamatos/farmacología
4.
Mol Ther ; 30(2): 798-815, 2022 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-34563674

RESUMEN

Spontaneous recovery after a stroke accounts for a significant part of the neurological recovery in patients. However limited, the spontaneous recovery is mechanistically driven by axonal restorative processes for which several molecular cues have been previously described. We report the acceleration of spontaneous recovery in a preclinical model of ischemia/reperfusion in rats via a single intracerebroventricular administration of extracellular vesicles released from primary cortical astrocytes. We used magnetic resonance imaging and confocal and multiphoton microscopy to correlate the structural remodeling of the corpus callosum and striatocortical circuits with neurological performance during 21 days. We also evaluated the functionality of the corpus callosum by repetitive recordings of compound action potentials to show that the recovery facilitated by astrocytic extracellular vesicles was both anatomical and functional. Our data provide compelling evidence that astrocytes can hasten the basal recovery that naturally occurs post-stroke through the release of cellular mediators contained in extracellular vesicles.


Asunto(s)
Vesículas Extracelulares , Accidente Cerebrovascular , Animales , Astrocitos , Axones , Modelos Animales de Enfermedad , Humanos , Imagen por Resonancia Magnética , Ratas , Recuperación de la Función/fisiología , Accidente Cerebrovascular/patología
5.
Neurobiol Learn Mem ; 193: 107647, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35679998

RESUMEN

Currently, it is widely accepted that memory extinction involves the formation of a new associative memory rather than unlearning of the information previously acquired. Nonetheless, the cellular and molecular mechanisms underlying this process are still unclear. In this regard, it has been suggested that while kinases modulate conditioning and LTP, phosphatases are relevant for extinction and LTD. In particular, the protein phosphatase calcineurin (CaN) has been involved in the extinction of some behavioral tasks along with LTD. Indeed, studies of our research group have demonstrated that induction of LTD in the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) pathway facilitates the extinction of conditioned taste aversion (CTA), while the induction of LTP in this pathway slows it down. In addition, we have shown that the extinction of CTA elicits an increase of CaN. The aim of the present study was to evaluate the participation of calcineurin in the extinction of CTA and in the expression of in vivo LTD in the Bla-IC pathway. For this purpose, we chemically inhibited calcineurin in the IC of adult male Wistar rats, either during CTA-extinction or thirty minutes after LTD induction in the Bla-IC pathway. Our results show that calcineurin inhibition slows down the CTA-extinction and blocks the maintenance of LTD. Furthermore, we show that CaN levels increase after LTD induction. These findings support the idea that calcineurin is a key molecular actor for both CTA extinction and LTD expression in the IC, a highly relevant neocortical area for the processing of aversively motivated learning tasks, suggesting that both processes are associated at a molecular level.


Asunto(s)
Reacción de Prevención , Calcineurina , Animales , Reacción de Prevención/fisiología , Calcineurina/metabolismo , Corteza Cerebral/fisiología , Corteza Insular , Masculino , Ratas , Ratas Wistar , Gusto/fisiología
6.
Neural Plast ; 2022: 7432842, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36213614

RESUMEN

The dentate gyrus (DG) is the gateway of sensory information arriving from the perforant pathway (PP) to the hippocampus. The adequate integration of incoming information into the DG is paramount in the execution of hippocampal-dependent cognitive functions. An abnormal DG granule cell layer (GCL) widening due to granule cell dispersion has been reported under hyperexcitation conditions in animal models as well as in patients with mesial temporal lobe epilepsy, but also in patients with no apparent relation to epilepsy. Strikingly, it is unclear whether the presence and severity of GCL widening along time affect synaptic processing arising from the PP and alter the performance in hippocampal-mediated behaviors. To evaluate the above, we injected excitotoxic kainic acid (KA) unilaterally into the DG of mice and analyzed the evolution of GCL widening at 10 and 30 days post injection (dpi), while analyzing if KA-induced GCL widening affected in vivo long-term potentiation (LTP) in the PP-DG pathway, as well as the performance in learning and memory through contextual fear conditioning. Our results show that at 10 dpi, when a subtle GCL widening was observed, LTP induction, as well as contextual fear memory, were impaired. However, at 30 dpi when a pronounced increase in GCL widening was found, LTP induction and contextual fear memory were already reestablished. These results highlight the plastic potential of the DG to recover some of its functions despite a major structural alteration such as abnormal GCL widening.


Asunto(s)
Giro Dentado , Potenciación a Largo Plazo , Animales , Cognición , Giro Dentado/metabolismo , Miedo , Ácido Kaínico/metabolismo , Ácido Kaínico/toxicidad , Potenciación a Largo Plazo/fisiología , Plásticos/metabolismo
7.
Neurobiol Learn Mem ; 182: 107449, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33915300

RESUMEN

Metaplasticity refers to the persistent modification, by previous activity, in the ability to induce synaptic plasticity. Accumulated evidence has proposed that metaplasticity contributes to network function and cognitive processes such as learning and memory. In this regard, it has been observed that training in several behavioral tasks modifies the possibility to induce subsequent synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD). For instance, our previous studies have shown that conditioned taste aversion (CTA) training prevents the induction of in vivo LTP in the projection from the basolateral nucleus of the amygdala to the insular cortex (BLA-IC). Likewise, we reported that extinction of CTA allows induction but not maintenance of LTP in the same pathway. Besides, we showed that it is possible to express in vivo low-frequency stimulation LTD in the BLA-IC projection and that its induction prior to CTA training facilitates the extinction of this task. However, until now, little is known about the participation of LTD on metaplastic processes. The present study aimed to analyze whether CTA training modifies the expression of in vivo LTD in the BLA-IC projection. To do so, animals received low-frequency stimulation to induce IC-LTD 48 h after CTA training. Our results show that CTA training occludes the subsequent induction of LTD in the BLA-IC pathway in a retrieval-dependent manner. These findings reveal that CTA elicits a metaplastic regulation of long-lasting changes in the IC synaptic strength, as well as that specific phases of learning differentially take part in adjusting the expression of synaptic plasticity in neocortical regions.


Asunto(s)
Reacción de Prevención/fisiología , Complejo Nuclear Basolateral/fisiología , Corteza Insular/fisiología , Depresión Sináptica a Largo Plazo/fisiología , Gusto , Animales , Extinción Psicológica/fisiología , Neocórtex/fisiología , Vías Nerviosas/fisiología , Plasticidad Neuronal/fisiología , Ratas
8.
Neurobiol Learn Mem ; 167: 107125, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31770584

RESUMEN

Brain-derived neurotrophic factor (BDNF) is an essential product of protein synthesis with a prominent impact on brain signaling and synaptic plasticity. Exogenous application of this neurotrophin is able to induce long-term potentiation (LTP) in several brain structures such as the hippocampus along with increases in gene transcription and translation of proteins involved in functional and structural plasticity. In this regard, our previous studies have demonstrated that acute intrahippocampal administration of BDNF induces long-lasting enhancement of synaptic transmission at the mossy fibers projection (MF) accompanied by a structural reorganization at the CA3 hippocampus area. Thus, considering the non-canonical molecular mechanisms underlying MF-CA3-LTP and the high expression of this neurotrophin in the CA3 area, we wonder whether transcriptional and translational inhibition interferes with the persistence of the MF functional and structural synaptic plasticity elicited by BDNF in adult rats in vivo. Our results show that BDNF is able to induce a lasting potentiation of synaptic efficacy at the MF projection accompanied by a structural reorganization at the CA3 area in an mRNA synthesis and protein translation-independent manner. The present findings support the idea that BDNF is an essential plasticity related product, which is necessary and sufficient to induce and maintain functional and structural synaptic plasticity at the MF-CA3 pathway.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Región CA3 Hipocampal/metabolismo , Potenciación a Largo Plazo , Fibras Musgosas del Hipocampo/metabolismo , Transmisión Sináptica , Animales , Factor Neurotrófico Derivado del Encéfalo/administración & dosificación , Región CA3 Hipocampal/fisiología , Expresión Génica , Masculino , ARN Mensajero/metabolismo , Ratas Wistar
9.
Neurobiol Learn Mem ; 154: 54-61, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29631000

RESUMEN

Accumulating evidence indicates that homeostatic plasticity mechanisms dynamically adjust synaptic strength to promote stability that is crucial for memory storage. Our previous studies have shown that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of long-term potentiation (LTP) in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) in vivo. We have also reported that induction of LTP in the Bla-IC pathway modifies the CTA extinction. Memoryextinction involves the formation of a new associativememorythat inhibits a previously conditioned association. The aim of the present study was to analyze the effect of CTA extinction on the ability to induce subsequent LTP in the Bla-IC projection in vivo. Thus, 48 h after CTA extinction animals received high frequency stimulation in order to induce IC-LTP. Our results show that extinction training allows the induction but not the maintenance of IC-LTP. In addition, with the purpose of exploring part of the mechanisms involved in this process and since a body of evidence suggests that protein phosphatase calcineurin (CaN) is involved in the extinction of some behavioral tasks, we analyzed the participation of this phosphatase. The present results show that extinction training increases the CaN expression in the IC, as well as that the inhibition of this phosphatase reverts the effects of the CTA-extinction on the IC-LTP. These findings reveal that CTA extinction promotes a homeostatic regulation of subsequent IC synaptic plasticity maintenance through increases in CaN levels.


Asunto(s)
Reacción de Prevención/fisiología , Calcineurina/fisiología , Corteza Cerebral/fisiología , Extinción Psicológica/fisiología , Potenciación a Largo Plazo , Memoria/fisiología , Animales , Complejo Nuclear Basolateral/fisiología , Masculino , Vías Nerviosas/fisiología , Ratas Wistar , Gusto , Percepción del Gusto
10.
Arch Toxicol ; 92(3): 1037-1048, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29204679

RESUMEN

Early life exposure to environmental pollutants and toxic chemicals has been linked to learning and behavioral alterations in children. iAs exposure is associated with different types neurological disorders such as memory and learning impairment. iAs is methylated in the brain by the arsenic III-methyltransferase in a process that requires glutathione (GSH). The xCT-antiporter cell membrane transporter participates in the influx of cystine for GSH synthesis in exchange for glutamate in a 1:1 ratio. In CD-1 mice gestationally exposed to 20 ppm of sodium arsenite in drinking water, we have previously observed up-regulation of xCT in the male mouse hippocampus which caused glutamatergic synapse alterations affecting learning and memory processes. Here, we used the same gestational iAs exposure model to investigate whether the up-regulation of xCT and down-regulation of GLT-1 transporters were associated with higher levels of extracellular glutamate and changes in the expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor, responsible for excitatory fast synaptic transmission. The induction of LTP in the perforant-dentate gyrus pathway (PP-DG) of the hippocampus was also studied, as well as learning and memory formation using the water maze test. Changes in GSH levels were also tested in the hippocampus of animals exposed to iAs. Results showed increased GSH synthesis (p < 0.05), associated with significantly higher extracellular glutamate levels in iAs exposed mice. Exposure was also significantly associated with AMPA subunits down-regulation, deficient LTP induction, and lower excitability of the PP-DG pathway. In addition, animals showed deficient learning and memory in the Morris Water Maze test.


Asunto(s)
Arsénico/toxicidad , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Receptores de Glutamato/metabolismo , Animales , Giro Dentado/efectos de los fármacos , Giro Dentado/metabolismo , Femenino , Glutatión/metabolismo , Hipocampo/metabolismo , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Trastornos de la Memoria/etiología , Ratones Endogámicos , Vía Perforante/efectos de los fármacos , Embarazo , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico/metabolismo
11.
Neurobiol Learn Mem ; 142(Pt A): 85-90, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28034786

RESUMEN

The history of activity of a given neuron has been proposed to bidirectionally influence its future response to synaptic inputs. In particular, induction of synaptic plasticity expressions such as long-term potentiation (LTP) and long-term depression (LTD) modifies the performance of several behavioral tasks. Our previous studies in the insular cortex (IC), a neocortical region that has been related to acquisition and retention of conditioned taste aversion (CTA), have demonstrated that induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC pathway before CTA training enhances the retention of this task. In addition, we reported that CTA training triggers a persistent impairment in the ability to induce in vivo LTP in the IC. The aim of the present study was to investigate whether LTD can be induced in the Bla-IC projection in vivo, as well as, whether the extinction of CTA is bidirectionally modified by previous synaptic plasticity induction in this pathway. Thus, rats received 900 train pulses (five 250µs pulses at 250Hz) delivered at 1Hz in the Bla-IC projection in order to induce LTD or 10 trains of 100Hz/1s with an intertrain interval of 20s in order to induce LTP. Seven days after surgery, rats were trained in the CTA task including the extinction trials. Our results show that the Bla-IC pathway is able to express in vivo LTD in an N-Methyl-D-aspartate (NMDA) receptor-dependent manner. Induction of LTD in the Bla-IC projection previous to CTA training facilitates the extinction of this task. Conversely, LTP induction enhances CTA retention. The present results show the bidirectional modulation of CTA extinction in response to IC-LTP and LTD, providing evidence of the homeostatic adaptation of taste learning.


Asunto(s)
Reacción de Prevención/fisiología , Corteza Cerebral/fisiología , Condicionamiento Clásico/fisiología , Extinción Psicológica/fisiología , Potenciación a Largo Plazo/fisiología , Depresión Sináptica a Largo Plazo/fisiología , Gusto/fisiología , Animales , Masculino , Ratas , Ratas Wistar
12.
Neurobiol Learn Mem ; 139: 56-62, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28039086

RESUMEN

CaMKII has been proposed as a molecular substrate for long-term memory storage due to its capacity to maintain an active autophosporylated state even after the decay of the external stimuli. The hippocampal mossy fiber-CA3 pathway (MF-CA3) is considered as a relevant area for acquisition and storage of different learning tasks. MF-CA3 pathway exhibits a form of LTP characterized by a slow initial increase in the EPSP slope that is independent of NMDA receptors activation. Our previous studies show that application of high frequency stimulation sufficient to elicit MF-CA3 LTP produces structural reorganization, in a manner independent of LTP induction, at the stratum oriens of hippocampal CA3 area 7days after stimulation. However, the molecular mechanisms that underlie the maintenance of MF-CA3 LTP as well as the concomitant structural reorganization in this area remain to be elucidated. Here we show that acute microinfusion of myr-CaMKIINtide, a noncompetitive inhibitor of CaMKII, in the hippocampal CA3 area of adult rats during the late-phase of in vivo MF-CA3 LTP blocked its maintenance and prevented the accompanying morphological reorganization in CA3 area. These findings support the idea that CaMKII is a key molecular substrate for the long-term hippocampal synaptic plasticity maintenance.


Asunto(s)
Región CA3 Hipocampal/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Fibras Musgosas del Hipocampo/metabolismo , Plasticidad Neuronal/fisiología , Animales , Región CA3 Hipocampal/efectos de los fármacos , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Masculino , Fibras Musgosas del Hipocampo/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Fosforilación/efectos de los fármacos , Ratas , Ratas Wistar
13.
Neurobiol Learn Mem ; 130: 71-6, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26854904

RESUMEN

Homeostatic plasticity mechanisms dynamically adjust synaptic strengths to promote stability that is crucial for memory storage. Metaplasticity is an example of these forms of plasticity that modify the capacity of synapses to experience subsequent Hebbian modifications. In particular, training in several behavioral tasks modifies the ability to induce long-term potentiation (LTP). Recently, we have reported that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP generated by high frequency stimulation in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC). One of the key molecular players that underlie long-term synaptic plasticity is brain-derived neurotrophic factor (BDNF). Previous studies from our group reported that acute microinfusion of BDNF in the IC induces a lasting potentiation of synaptic efficacy at the Bla-IC projection. Thus, the aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent BDNF-induced potentiation of synaptic transmission in the Bla-IC projection in vivo. Accordingly, CTA trained rats received intracortical microinfusion of BDNF in order to induce lasting potentiation 48h after the aversion test. Our results show that CTA training prevents the induction of in vivo BDNF-LTP in the Bla-IC projection. The present results provide evidence that CTA modulates BDNF-dependent changes in IC synaptic strength.


Asunto(s)
Reacción de Prevención/fisiología , Factor Neurotrófico Derivado del Encéfalo/farmacología , Corteza Cerebral/efectos de los fármacos , Condicionamiento Clásico/fisiología , Plasticidad Neuronal/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Gusto/fisiología , Animales , Corteza Cerebral/fisiología , Masculino , Plasticidad Neuronal/fisiología , Ratas , Ratas Wistar , Transmisión Sináptica/fisiología , Percepción del Gusto/fisiología
14.
Neurobiol Learn Mem ; 116: 139-44, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25451308

RESUMEN

Brain-derived neurotrophic factor (BDNF) has emerged as one of the most potent molecular mediators not only for synaptic plasticity, but also for the behavioral organism-environment interactions. Our previous studies in the insular cortex (IC), a neocortical region that has been related with acquisition and retention of conditioned taste aversion (CTA), have demonstrated that intracortical microinfusion of BDNF induces a lasting potentiation of synaptic efficacy in the basolateral amygdaloid nucleus (Bla)-IC projection and enhances the retention of CTA memory of adult rats in vivo. The aim of the present study was to analyze whether acute BDNF-infusion in the IC modifies the extinction of CTA. Accordingly, animals were trained in the CTA task and received bilateral IC microinfusions of BDNF before extinction training. Our results showed that taste aversion was significantly reduced in BDNF rats from the first extinction trial. Additionally, we found that the effect of BDNF on taste aversion did not require extinction training. Finally we showed that the BDNF effect does not degrade the original taste aversion memory trace. These results emphasize that BDNF activity underlies memory extinction in neocortical areas and support the idea that BDNF is a key regulator and mediator of long-term synaptic modifications.


Asunto(s)
Reacción de Prevención/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/farmacología , Corteza Cerebral/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Extinción Psicológica/efectos de los fármacos , Gusto/efectos de los fármacos , Animales , Masculino , Ratas , Ratas Wistar
15.
Behav Brain Res ; 461: 114857, 2024 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-38211776

RESUMEN

Memory consolidation is an essential process of long-term memory formation. Neurotrophins have been suggested as key regulators of activity dependent changes in the synaptic efficacy and morphology, which are considered the downstream mechanisms of memory consolidation. The neurotrophin 3 (NT-3), a member of the neurotrophin family, and its high affinity receptor TrkC, are widely expressed in the insular cortex (IC), a region with a critical role in the consolidation of the conditioned taste aversion (CTA) paradigm, in which an animal associates a novel taste with nausea. Nevertheless, the role of this neurotrophin in the cognitive processes that the IC mediates remains unexamined. To answer whether NT-3 is involved in memory consolidation at the IC, adult male Wistar rats were administered with NT-3 or NT-3 in combination with the Trk receptors inhibitor K252a into the IC, immediately after CTA acquisition under two different conditions: a strong-CTA (0.2 M lithium chloride i.p.) or a weak-CTA (0.1 M lithium chloride i.p.). Our results show that NT-3 strengthens the memory trace of CTA, transforming a weak conditioning into a strong one, in a Trk-dependent manner. The present evidence suggests that NT-3 has a key role in the consolidation process of an aversive memory in a neocortical region.


Asunto(s)
Corteza Cerebral , Corteza Insular , Ratas , Animales , Masculino , Ratas Wistar , Gusto , Cloruro de Litio/farmacología , Neurotrofina 3 , Reacción de Prevención
16.
Hippocampus ; 22(1): 1-8, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20848610

RESUMEN

Changes in synaptic efficacy and morphology have been proposed as mechanisms underlying learning and memory processes. In our previous studies, high frequency stimulation (HFS) sufficient to induce LTP at the hippocampal mossy fiber (MF) pathway, leads to MF synaptogenesis, in a prominent contralateral form, at the stratum oriens of hippocampal CA3 area. Recently we reported that acute intrahippocampal microinfusion of BDNF induces a lasting potentiation of synaptic efficacy at the MF projection accompanied by a structural reorganization at the CA3 area within the stratum oriens region in a prominent ipsilateral form. It is considered that the capacity of synapses to express plastic changes is itself subject to variation dependent on previous experience. Here we used intrahippocampal microinfusion of BDNF to analyze its effects on functional and structural synaptic plasticity induced by subsequent mossy fiber HFS sufficient to induce LTP in adult rats, in vivo. Our results show that BDNF modifies the ability of the MF pathway to present LTP by HFS. Moreover BDNF modified the structural reorganization pattern produced by HFS, presenting a balanced bilateral appearance. Microinfusion of K252a blocks the functional and morphological effects produced by BDNF, revealing that the BDNF modulation is dependent on its TrkB receptor activation. These findings support the idea that BDNF actions modify subsequent synaptic plasticity; a homeostatic mechanism thought to be essential for synaptic integration among prolonged temporal domains in the adult mammalian brain.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/fisiología , Fibras Musgosas del Hipocampo/fisiología , Plasticidad Neuronal/fisiología , Transmisión Sináptica/fisiología , Animales , Región CA3 Hipocampal/efectos de los fármacos , Región CA3 Hipocampal/fisiología , Carbazoles/administración & dosificación , Estimulación Eléctrica/métodos , Homeostasis/efectos de los fármacos , Homeostasis/fisiología , Alcaloides Indólicos/administración & dosificación , Potenciación a Largo Plazo/efectos de los fármacos , Potenciación a Largo Plazo/fisiología , Masculino , Microinyecciones/métodos , Fibras Musgosas del Hipocampo/efectos de los fármacos , Fibras Musgosas del Hipocampo/metabolismo , Plasticidad Neuronal/efectos de los fármacos , Ratas , Ratas Wistar , Transmisión Sináptica/efectos de los fármacos
17.
Rev Neurosci ; 23(5-6): 473-80, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23096103

RESUMEN

The activity history of a given neuron or pathway has been suggested to influence its future responses to synaptic inputs. In particular, training in several learning tasks produces a metaplastic change, that is, a change in the ability to induce subsequent synaptic plasticity. Experimental evidence shows that the maintenance of long term memory and long-term potentiation (LTP) requires the persistent action of the atypical protein kinase Cisoform, protein kinase M ζ (PKM ζ ). Recent work has demonstrated that the inactivation of PKM ζ in the insular cortex (IC) abolishes conditioned taste aversion (CTA) long term memory. Our previous studies in the IC have demonstrated that the induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC projection previous to CTA training enhances the retention of this task. Moreover, recently, we have observed that CTA training blocks the subsequent induction of LTP in the Bla-IC projection. The aim of the present study was to investigate the participation of PKM ζon the CTA-dependent modification of the ability to induce subsequent LTP in the Bla-IC projection in vivo . Thus, we have delivered high-frequency stimulation in the Bla-IC projection in order to induce in vivo IC-LTP in the rats that underwent or did not have an impairment of CTA retention due to the intracortical administration of the selective PKM ζ pseudosubstrate inhibitory peptide, ZIP. Our results show that the microinfusion of ZIP into the IC of the behaving rats impairs long-term memory of CTA and prevents its effects on IC-LTP. These results indicate that PKM ζ is a key component of the cellular mechanisms necessary for the persistence of lasting memory traces as well as for those underlying metaplastic changes in neocortex, contributing to the persistence of aversive memories.


Asunto(s)
Reacción de Prevención/fisiología , Corteza Cerebral/metabolismo , Potenciación a Largo Plazo/fisiología , Proteína Quinasa C/metabolismo , Gusto/fisiología , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/fisiología , Análisis de Varianza , Animales , Reacción de Prevención/efectos de los fármacos , Biofisica , Condicionamiento Psicológico/efectos de los fármacos , Condicionamiento Psicológico/fisiología , Estimulación Eléctrica , Inhibidores Enzimáticos/farmacología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiología , Oligopéptidos/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Ratas , Ratas Wistar , Gusto/efectos de los fármacos
18.
Behav Brain Res ; 430: 113947, 2022 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-35644274

RESUMEN

It has been shown that exposure to an enriched environment (EE) can modulate the physiological impact of aversive stimuli in animals, promoting adaptive attitudes, as well as the development of resilience to stressful situations. These changes are known to be related to increased levels of some trophic factors, such as brain-derived neurotrophic factor (BDNF), which has been considered a regulatory protein for synaptic plasticity in the adult brain. Our previous studies have demonstrated that in the insular cortex (IC), a brain region of the temporal lobe implicated in the acquisition, consolidation, and retention of conditioned taste aversion (CTA) task, BDNF can reverse the CTA memory deficit caused by a protein synthesis inhibitor. Likewise, our research group have also shown that BDNF is required for the maintenance of CTA long-term memory. Here we evaluate the effects of the exposure to an enriched environment on the CTA memory strength, using a weak and strong version of this paradigm. The exposure to an EE for 21 days was able to attenuate the strong-CTA response through the restoration of BDNF levels in the IC of adult rats. These results provide evidence that environmental enrichment is capable of reducing the strength of an aversive memory trace, restoring the BDNF levels in a neocortical region of the adult brain.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/metabolismo , Gusto , Animales , Reacción de Prevención , Corteza Cerebral/fisiología , Corteza Insular , Ratas , Ratas Wistar
19.
Neurobiol Learn Mem ; 95(4): 519-26, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21440652

RESUMEN

The ability of neurons to modify their synaptic strength in an activity-dependent manner has a crucial role in learning and memory processes. It has been proposed that homeostatic forms of plasticity might provide the global regulation necessary to maintain synaptic strength and plasticity within a functional dynamic range. Similarly, it is considered that the capacity of synapses to express plastic changes is itself subject to variation dependent on previous experience. In particular, training in several behavioral tasks modifies the possibility to induce long-term potentiation (LTP). Our previous studies in the insular cortex (IC) have shown that induction of LTP in the basolateral amygdaloid nucleus (Bla)-IC projection previous to conditioned taste aversion (CTA) training enhances the retention of this task. The aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent LTP in the Bla-IC projection in vivo. Thus, CTA trained rats received high frequency stimulation in the Bla-IC projection in order to induce LTP 48, 72, 96 and 120 h after the aversion test. Our results show that CTA training prevents the subsequent induction of LTP in the Bla-IC projection, for at least 120 h after CTA training. We also showed that pharmacological inhibition of CTA consolidation with anisomycin (1 µl/side; 100 µg/µl) prevents the CTA effect on IC-LTP. These findings reveal that CTA training produces a persistent change in the ability to induce subsequent LTP in the Bla-IC projection in a protein-synthesis dependent manner, suggesting that changes in the ability to induce subsequent synaptic plasticity contribute to the formation and persistence of aversive memories.


Asunto(s)
Amígdala del Cerebelo/fisiología , Reacción de Prevención/fisiología , Condicionamiento Clásico/fisiología , Potenciación a Largo Plazo/fisiología , Inhibición Neural/fisiología , Transmisión Sináptica/fisiología , Animales , Masculino , Neocórtex/fisiología , Ratas , Ratas Wistar , Retención en Psicología/fisiología , Gusto
20.
Front Cell Neurosci ; 15: 685838, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34220454

RESUMEN

In nature, animals need to adapt to constant changes in their environment. Learning and memory are cognitive capabilities that allow this to happen. Extinction, the reduction of a certain behavior or learning previously established, refers to a very particular and interesting type of learning that has been the basis of a series of therapies to diminish non-adaptive behaviors. In recent years, the exploration of the cellular and molecular mechanisms underlying this type of learning has received increasing attention. Hebbian plasticity (the activity-dependent modification of the strength or efficacy of synaptic transmission), and homeostatic plasticity (the homeostatic regulation of plasticity) constitute processes intimately associated with memory formation and maintenance. Particularly, long-term depression (LTD) has been proposed as the underlying mechanism of extinction, while the protein phosphatase calcineurin (CaN) has been widely related to both the extinction process and LTD. In this review, we focus on the available evidence that sustains CaN modulation of LTD and its association with extinction. Beyond the classic view, we also examine the interconnection among extinction, Hebbian and homeostatic plasticity, as well as emergent evidence of the participation of kinases and long-term potentiation (LTP) on extinction learning, highlighting the importance of the balance between kinases and phosphatases in the expression of extinction. Finally, we also integrate data that shows the association between extinction and less-studied phenomena, such as synaptic silencing and engram formation that open new perspectives in the field.

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