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1.
STAR Protoc ; 4(3): 102414, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37436903

RESUMEN

Memory processes are highly dependent on a cross-talk between brain regions via synchronized neural oscillations. Here, we present a protocol to perform multi-site electrophysiological recordings in vivo in freely moving rodents to investigate functional connectivity across brain regions during memory processes. We describe steps for recording local field potentials (LFPs) during behavior, extracting LFP bands, and analyzing synchronized LFP activity across brain regions. This technique also provides the potential to simultaneously assess single unit activity using tetrodes. For complete details on the use and execution of this protocol, please refer to Wang et al.1.


Asunto(s)
Encéfalo , Roedores , Animales , Encéfalo/fisiología , Fenómenos Electrofisiológicos
2.
Curr Opin Neurobiol ; 80: 102712, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37003106

RESUMEN

Associative learning induces physical changes to a network of cells, known as the memory engram. Fear is widely used as a model to understand the circuit motifs that underpin associative memories. Recent advances suggest that the distinct circuitry engaged by different conditioned stimuli (e.g. tone vs. context) can provide insights into what information is being encoded in the fear engram. Moreover, as the fear memory matures, the circuitry engaged indicates how information is remodelled after learning and hints at potential mechanisms for consolidation. Finally, we propose that the consolidation of fear memories involves plasticity of engram cells through coordinated activity between brain regions, and the inherent characteristics of the circuitry may mediate this process.


Asunto(s)
Aprendizaje , Memoria , Condicionamiento Clásico , Miedo
3.
iScience ; 25(10): 105036, 2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36147953

RESUMEN

Fear learning, and its extinction, are fundamental learning processes that allow for a response adaptation to aversive events and threats in the environment. Thus, it is critical to understand the neural mechanism that underpins fear learning and its relapse following extinction. The neural dynamics within the subregions of the medial prefrontal cortex, including the prelimbic cortex (PL) and the infralimbic (IL) cortex, and functional connectivity between them during fear extinction and its relapse, are not well understood. Using in-vivo electrophysiological recordings in awake behaving rats, we identified increased theta activity in the PL during fear learning and in the IL following extinction. Importantly, the PL-IL theta coupling is significantly enhanced throughout fear learning and extinction, but not in fear relapse. Together, our results provide evidence for the importance of synchronized PL-IL activity to regulate context-dependent retrieval of a fear extinction memory.

4.
J Neurosci ; 41(46): 9617-9632, 2021 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-34642213

RESUMEN

Recognition memory provides the ability to distinguish familiar from novel objects and places, and is important for recording and updating events to guide appropriate behavior. The hippocampus (HPC) and medial prefrontal cortex (mPFC) have both been implicated in recognition memory, but the nature of HPC-mPFC interactions, and its impact on local circuits in mediating this process is not known. Here we show that novelty discrimination is accompanied with higher theta activity (4-10 Hz) and increased c-Fos expression in both these regions. Moreover, theta oscillations were highly coupled between the HPC and mPFC during recognition memory retrieval for novelty discrimination, with the HPC leading the mPFC, but not during initial learning. Principal neurons and interneurons in the mPFC responded more strongly during recognition memory retrieval compared with learning. Optogenetic silencing of HPC input to the mPFC disrupted coupled theta activity between these two structures, as well as the animals' (male Sprague Dawley rats) ability to differentiate novel from familiar objects. These results reveal a key role of monosynaptic connections between the HPC and mPFC in novelty discrimination via theta coupling and identify neural populations that underlie this recognition memory-guided behavior.SIGNIFICANCE STATEMENT Many memory processes are highly dependent on the interregional communication between the HPC and mPFC via neural oscillations. However, how these two brain regions coordinate their oscillatory activity to engage local neural populations to mediate recognition memory for novelty discrimination is poorly understood. This study revealed that the HPC and mPFC theta oscillations and their temporal coupling is correlated with recognition memory-guided behavior. During novel object recognition, the HPC drives mPFC interneurons to effectively reduce the activity of principal neurons. This study provides the first evidence for the requirement of the HPC-mPFC pathway to mediate recognition memory for novelty discrimination and describes a mechanism for how this memory is regulated.


Asunto(s)
Aprendizaje Discriminativo/fisiología , Hipocampo/fisiología , Memoria/fisiología , Corteza Prefrontal/fisiología , Reconocimiento en Psicología/fisiología , Animales , Masculino , Vías Nerviosas/fisiología , Neuronas/fisiología , Ratas , Ratas Sprague-Dawley
5.
Psychopharmacology (Berl) ; 236(1): 313-320, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30215217

RESUMEN

Fear learning and extinction are controlled by the activity of three interconnected regions: the amygdala, hippocampus, and prefrontal cortex. Of these, the medial prefrontal cortex modulates specific aspects in fear and extinction via a top-down regulation. In recent years, extensive progress has been made in our understanding of the neural circuits that mediate fear-related behaviors and their modulation by ascending systems. The development of new experimental techniques is now revealing the details of the intrinsic circuits within these structures as well as the connections between them. Here, we highlight recent advances in our understanding of how the prefrontal cortex may mediate such a top-down regulation.


Asunto(s)
Amígdala del Cerebelo/fisiología , Extinción Psicológica/fisiología , Miedo/fisiología , Hipocampo/fisiología , Red Nerviosa/fisiología , Corteza Prefrontal/fisiología , Animales , Condicionamiento Clásico/fisiología , Giro del Cíngulo/fisiología , Humanos , Recuerdo Mental/fisiología , Neuronas/fisiología , Primates , Retención en Psicología/fisiología , Roedores , Tálamo/fisiología
6.
Adv Neurobiol ; 21: 35-48, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30334218

RESUMEN

The activity of neural circuits that underpin particular behaviours are one of the most interesting questions in neurobiology today. This understanding will not only lead to a detailed understanding of learning and memory formation, but also provides a platform for the development of novel therapeutic approaches to a range of neurological disorders that afflict humans. Among the different behavioural paradigms, Pavlovian fear conditioning and its extinction are two of the most extensively used to study acquisition, consolidation and retrieval of fear-related memories. The amygdala, medial prefrontal cortex (mPFC) and hippocampus are three regions with extensive bidirectional connections, and play key roles in fear processing. In this chapter, we summarise our current understanding of the structure and physiological role of these three regions in fear learning and extinction.


Asunto(s)
Extinción Psicológica , Miedo , Amígdala del Cerebelo/fisiología , Condicionamiento Clásico , Hipocampo/fisiología , Humanos , Corteza Prefrontal/fisiología
7.
Nat Neurosci ; 21(9): 1291, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29988070

RESUMEN

In the version of this article initially published, the traces in Fig. 1j and in Fig. 1k, right, were duplicated from the corresponding traces in Fig. 1c, bottom, and Fig. 1d, bottom right. The error has been corrected in the HTML and PDF versions of the article.

8.
Nat Neurosci ; 21(5): 654-658, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29686260

RESUMEN

We elucidated the intrinsic circuitry of the medial prefrontal cortex and its role in regulating fear extinction, using neuronal tracing and optogenetic stimulation in vitro and in vivo. We show that pyramidal neurons in layer 5/6 of the prelimbic medial prefrontal cortex project to pyramidal cells in layer 5/6 of the infralimbic cortex. Activation of this connection enhances fear extinction, redefining the role of the prelimbic cortex in extinction learning.


Asunto(s)
Extinción Psicológica/fisiología , Miedo/fisiología , Sistema Límbico/fisiología , Vías Nerviosas/fisiología , Corteza Prefrontal/fisiología , Animales , Mapeo Encefálico , Femenino , Aprendizaje/fisiología , Sistema Límbico/citología , Masculino , Vías Nerviosas/citología , Neuronas Aferentes/fisiología , Optogenética , Técnicas de Placa-Clamp , Corteza Prefrontal/citología , Células Piramidales/fisiología , Ratas , Ratas Sprague-Dawley , Ratas Wistar
9.
Nat Neurosci ; 21(3): 384-392, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29403033

RESUMEN

The medial prefrontal cortex (mPFC) has been implicated in the extinction of emotional memories, including conditioned fear. We found that ventral hippocampal (vHPC) projections to the infralimbic (IL) cortex recruited parvalbumin-expressing interneurons to counter the expression of extinguished fear and promote fear relapse. Whole-cell recordings ex vivo revealed that optogenetic activation of vHPC input to amygdala-projecting pyramidal neurons in the IL was dominated by feed-forward inhibition. Selectively silencing parvalbumin-expressing, but not somatostatin-expressing, interneurons in the IL eliminated vHPC-mediated inhibition. In behaving rats, pharmacogenetic activation of vHPC→IL projections impaired extinction recall, whereas silencing IL projectors diminished fear renewal. Intra-IL infusion of GABA receptor agonists or antagonists, respectively, reproduced these effects. Together, our findings describe a previously unknown circuit mechanism for the contextual control of fear, and indicate that vHPC-mediated inhibition of IL is an essential neural substrate for fear relapse.


Asunto(s)
Extinción Psicológica/fisiología , Miedo/fisiología , Hipocampo/fisiología , Corteza Prefrontal/fisiología , Amígdala del Cerebelo/citología , Amígdala del Cerebelo/fisiología , Animales , Interneuronas/fisiología , Masculino , Parvalbúminas/metabolismo , Técnicas de Placa-Clamp , Ratas , Ratas Wistar , Receptores de GABA/fisiología , Somatostatina/metabolismo
10.
Cell Rep ; 10(9): 1435-1442, 2015 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-25753409

RESUMEN

The basolateral amygdala (BLA) and prefrontal cortex (PFC) are partners in fear learning and extinction. Intercalated (ITC) cells are inhibitory neurons that surround the BLA. Lateral ITC (lITC) neurons provide feed-forward inhibition to BLA principal neurons, whereas medial ITC (mITC) neurons form an inhibitory interface between the BLA and central amygdala (CeA). Notably, infralimbic prefrontal (IL) input to mITC neurons is thought to play a key role in fear extinction. Here, using targeted optogenetic stimulation, we show that lITC neurons receive auditory input from cortical and thalamic regions. IL inputs innervate principal neurons in the BLA but not mITC neurons. These results suggest that (1) these neurons may play a more central role in fear learning as both lITCs and mITCs receive auditory input and that (2) mITC neurons cannot be driven directly by the IL, and their role in fear extinction is likely mediated via the BLA.

11.
Neuron ; 82(6): 1289-98, 2014 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-24945772

RESUMEN

Bilateral integration of sensory and associative brain processing is achieved by precise connections between homologous regions in the two hemispheres via the corpus callosum. These connections form postnatally, and unilateral deprivation of sensory or spontaneous cortical activity during a critical period severely disrupts callosal wiring. However, little is known about how this early activity affects precise circuit formation. Here, using in utero electroporation of reporter genes, optogenetic constructs, and direct disruption of activity in callosal neurons combined with whisker ablations, we show that balanced interhemispheric activity, and not simply intact cortical activity in either hemisphere, is required for functional callosal targeting. Moreover, bilateral ablation of whiskers in symmetric or asymmetric configurations shows that spatially symmetric interhemispheric activity is required for appropriate callosal targeting. Our findings reveal a principle governing axon targeting, where spatially balanced activity between regions is required to establish their appropriate connectivity.


Asunto(s)
Potenciales de Acción/fisiología , Cuerpo Calloso/fisiología , Lateralidad Funcional/fisiología , Animales , Animales Recién Nacidos , Femenino , Ratones , Vías Nerviosas/fisiología , Embarazo
12.
J Physiol ; 591(10): 2381-91, 2013 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-23420655

RESUMEN

Fear conditioning and fear extinction are Pavlovian conditioning paradigms extensively used to study the mechanisms that underlie learning and memory formation. The neural circuits that mediate this learning are evolutionarily conserved, and seen in virtually all species from flies to humans. In mammals, the amygdala and medial prefrontal cortex are two structures that play a key role in the acquisition, consolidation and retrieval of fear memory, as well extinction of fear. These two regions have extensive bidirectional connections, and in recent years, the neural circuits that mediate fear learning and fear extinction are beginning to be elucidated. In this review, we provide an overview of our current understanding of the neural architecture within the amygdala and medial prefrontal cortex. We describe how sensory information is processed in these two structures and the neural circuits between them thought to mediate different aspects of fear learning. Finally, we discuss how changes in circuits within these structures may mediate fear responses following fear conditioning and extinction.


Asunto(s)
Amígdala del Cerebelo/fisiología , Miedo/fisiología , Corteza Prefrontal/fisiología , Animales , Condicionamiento Clásico , Extinción Psicológica , Humanos
13.
Eur J Neurosci ; 37(6): 964-71, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23311402

RESUMEN

The central circadian pacemaker of the suprachiasmatic nuclei (SCN) is a bilaterally symmetrical structure. Little is known about the physiological mechanisms underlying communication between the left and right SCN and yet the degree of synchronization between SCN neurons can have a critical impact on the properties of the circadian system. In this study, we used electrophysiological tools and calcium (Ca(2+) ) imaging to examine the mechanisms underlying bilateral signaling in mouse SCN. Electrical stimulation of one SCN produced responses in the contralateral SCN with a short delay (approximately 5 ms) and Ca(2+) -dependence that are consistent with action potential-mediated chemical synaptic transmission. Patch-clamp recordings of stimulated cells revealed excitatory postsynaptic inward-currents (EPSCs), which were sufficient in magnitude to elicit action potentials. Electrical stimulation evoked tetrodotoxin-dependent Ca(2+) transients in about 30% of all contralateral SCN neurons recorded. The responding neurons were widely distributed within the SCN with a highest density in the posterior SCN. EPSCs and Ca(2+) responses were significantly reduced after application of a glutamate receptor antagonist. Application of antagonists for receptors of other candidate transmitters inhibited the Ca(2+) responses in some of the cells but overall the impact of these antagonists was variable. In a functional assay, electrical stimulation of the SCN produced phase shifts in the circadian rhythm in the frequency of multiunit activity rhythm in the contralateral SCN. These phase shifts were blocked by a glutamate receptor antagonist. Taken together, these results implicate glutamate as a transmitter required for communication between the left and right SCN.


Asunto(s)
Lateralidad Funcional , Núcleo Supraquiasmático/fisiología , Potenciales de Acción , Animales , Calcio/metabolismo , Señalización del Calcio , Ritmo Circadiano , Estimulación Eléctrica , Antagonistas de Aminoácidos Excitadores/farmacología , Potenciales Postsinápticos Excitadores , Ácido Glutámico/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/metabolismo , Neuronas/fisiología , Tiempo de Reacción , Receptores AMPA/antagonistas & inhibidores , Receptores AMPA/metabolismo , Núcleo Supraquiasmático/metabolismo
14.
J Neurosci ; 32(35): 11930-41, 2012 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-22933779

RESUMEN

It is well established that the activity of chromatin-modifying enzymes is crucial for regulating gene expression associated with hippocampal-dependent memories. However, very little is known about how these epigenetic mechanisms influence the formation of cortically dependent memory, particularly when there is competition between opposing memory traces, such as that which occurs during the acquisition and extinction of conditioned fear. Here we demonstrate, in C57BL/6 mice, that the activity of p300/CBP-associated factor (PCAF) within the infralimbic prefrontal cortex is required for long-term potentiation and is necessary for the formation of memory associated with fear extinction, but not for fear acquisition. Further, systemic administration of the PCAF activator SPV106 enhances memory for fear extinction and prevents fear renewal. The selective influence of PCAF on fear extinction is mediated, in part, by a transient recruitment of the repressive transcription factor ATF4 to the promoter of the immediate early gene zif268, which competitively inhibits its expression. Thus, within the context of fear extinction, PCAF functions as a transcriptional coactivator, which may facilitate the formation of memory for fear extinction by interfering with reconsolidation of the original memory trace.


Asunto(s)
Condicionamiento Psicológico/fisiología , Extinción Psicológica/fisiología , Miedo/fisiología , Factores de Transcripción p300-CBP/fisiología , Animales , Miedo/psicología , Células HEK293 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Transactivadores/fisiología
15.
J Neurosci ; 31(20): 7486-91, 2011 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-21593332

RESUMEN

It is well established that the coordinated regulation of activity-dependent gene expression by the histone acetyltransferase (HAT) family of transcriptional coactivators is crucial for the formation of contextual fear and spatial memory, and for hippocampal synaptic plasticity. However, no studies have examined the role of this epigenetic mechanism within the infralimbic prefrontal cortex (ILPFC), an area of the brain that is essential for the formation and consolidation of fear extinction memory. Here we report that a postextinction training infusion of a combined p300/CBP inhibitor (Lys-CoA-Tat), directly into the ILPFC, enhances fear extinction memory in mice. Our results also demonstrate that the HAT p300 is highly expressed within pyramidal neurons of the ILPFC and that the small-molecule p300-specific inhibitor (C646) infused into the ILPFC immediately after weak extinction training enhances the consolidation of fear extinction memory. C646 infused 6 h after extinction had no effect on fear extinction memory, nor did an immediate postextinction training infusion into the prelimbic prefrontal cortex. Consistent with the behavioral findings, inhibition of p300 activity within the ILPFC facilitated long-term potentiation (LTP) under stimulation conditions that do not evoke long-lasting LTP. These data suggest that one function of p300 activity within the ILPFC is to constrain synaptic plasticity, and that a reduction in the function of this HAT is required for the formation of fear extinction memory.


Asunto(s)
Extinción Psicológica/fisiología , Miedo/fisiología , Memoria/fisiología , Plasticidad Neuronal/fisiología , Sinapsis/enzimología , Factores de Transcripción p300-CBP/antagonistas & inhibidores , Animales , Extinción Psicológica/efectos de los fármacos , Miedo/efectos de los fármacos , Potenciación a Largo Plazo/efectos de los fármacos , Potenciación a Largo Plazo/fisiología , Masculino , Memoria/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Plasticidad Neuronal/efectos de los fármacos , Sinapsis/efectos de los fármacos , Factores de Transcripción p300-CBP/metabolismo
16.
Biol Psychiatry ; 66(3): 283-6, 2009 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-19306990

RESUMEN

BACKGROUND: Transcranial magnetic stimulation (TMS) is a noninvasive procedure that may be used to study individual differences in motor cortex excitability. Such differences are assumed to reflect serotonergic and other inputs to the motor cortex. METHODS: Here we investigate the impact of a functional polymorphism in the promoter region of the 5-hydroxytryptamine transporter gene (5-HTTLPR) on measures of motor cortex excitability. RESULTS: Sixty healthy subjects carrying one or two copies of the short 5-HTTLPR allele (s/s and s/l) showed a significant reduction in short intracortical inhibition (SICI, p = .012) and an increased cortical silent period (p = .042) compared with 60 age- and sex-matched individuals homozygous for the long allele (l/l). In contrast, motor threshold and intracortical facilitation did not differ significantly between groups. CONCLUSIONS: These results provide further evidence of a role for serotonergic transmission in the modulation of cortical excitability. Differential effects on the measures under study suggest a pattern of prioritization in bioamine regulation of cortical inhibition.


Asunto(s)
Alelos , Corteza Cerebral/fisiología , Depresión de Propagación Cortical/genética , Potenciales Evocados Motores/genética , Variación Genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adulto , Estudios de Casos y Controles , Electromiografía , Femenino , Lateralidad Funcional/fisiología , Humanos , Masculino , Tiempo de Reacción/fisiología , Factores de Tiempo , Estimulación Magnética Transcraneal , Adulto Joven
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