Fear potentiated startle increases phospholipase D (PLD) expression/activity and PLD-linked metabotropic glutamate receptor mediated post-tetanic potentiation in rat amygdala.

Long-term memory (LTM) of fear stores activity dependent modifications that include changes in amygdala signaling. Previously, we identified an enhanced probability of release of glutamate mediated signaling to be important in rat fear potentiated startle (FPS), a well-established translational behavioral measure of fear. Here, we investigated short- and long-term synaptic plasticity in FPS involving metabotropic glutamate receptors (mGluRs) and associated downstream proteomic changes in the thalamic-lateral amygdala pathway (Th-LA).

Dopamine-induced plasticity, phospholipase D (PLD) activity and cocaine-cue behavior depend on PLD-linked metabotropic glutamate receptors in amygdala.

Cocaine-cue associations induce synaptic plasticity with long lasting molecular and cellular changes in the amygdala, a site crucial for cue-associated memory mechanisms. The underlying neuroadaptations can include marked alterations in signaling via dopamine (DA) receptors (DRs) and metabotropic glutamate (Glu) receptors (mGluRs). Previously, we reported that DR antagonists blocked forms of synaptic plasticity in amygdala slices of Sprague-Dawley rats withdrawn from repeated cocaine administration.

Cocaine withdrawal reduces group I mGluR-mediated long-term potentiation via decreased GABAergic transmission in the amygdala.

Cocaine relapse can occur when cocaine-associated environmental cues induce craving. Conditioned place preference (CPP) is a behavioral paradigm modeling the association between cocaine exposure and environmental cues. The amygdala is involved in cocaine cue associations with the basolateral amygdala (BLA) and central amygdala (CeA) acting differentially in cue-induced relapse.

Dopamine receptor mechanisms mediate corticotropin-releasing factor-induced long-term potentiation in the rat amygdala following cocaine withdrawal.

Corticotropin-releasing factor (CRF) in the amygdala is involved in stress responses. Moreover, dopaminergic neurotransmission in the brain reward system including the amygdala plays a significant role in the pathology of cocaine addiction. The present study analysed CRF-induced synaptic plasticity, its pharmacological sensitivity and interactions with the dopamine (DA) system in the basolateral to lateral capsula central amygdala (lcCeA) pathway after a 2-week withdrawal from repeated cocaine administration.

Increased insertion of glutamate receptor 2-lacking alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors at hippocampal synapses upon repeated morphine administration.

Evidence suggests that the long-term adaptations in the hippocampus after repeated drug treatment may parallel its role during memory formation. The neuroplasticity that subserves learning and memory is also believed to underlie addictive processes. We have reported previously that repeated morphine administration alters local distribution of endocytic proteins at hippocampal synapses, which could in turn affect expression of glutamate receptors.

Synaptic physiology of central CRH system.

Corticotropin-Releasing Hormone (CRH) or Corticotropin-Releasing Factor (CRF) and its family of related naturally occurring endogenous peptides and receptors are becoming recognized for their actions within central (CNS) and peripheral (PNS) nervous systems. It should be recognized that the term 'CRH' has been displaced by 'CRF' [Guillemin, R., 2005.

Dopamine and corticotropin-releasing factor synergistically alter basolateral amygdala-to-medial prefrontal cortex synaptic transmission: functional switch after chronic cocaine administration.

Basolateral amygdala (BLA) neurons provide a major excitatory input to medial prefrontal cortex (mPFC)-layer V pyramidal neurons. Under stressful conditions, commonly associated with chronic cocaine abuse, altered BLA-to-mPFC synaptic transmission could lead to defective emotional information processing and decision making within the mPFC and result in misguided and inappropriate behaviors. We examined the effects of cocaine administered chronically in vivo on EPSCs recorded from a putative BLA-mPFC pathway in vitro and their modulation by dopamine (DA), corticotropin-releasing factor (CRF), and their combination (DA plus CRF).

Long-term potentiation (LTP) in the central amygdala (CeA) is enhanced after prolonged withdrawal from chronic cocaine and requires CRF1 receptors.

The amygdala is part of the brain reward circuitry that plays a role in cocaine-seeking and abstinence in animals and cocaine craving and relapse in humans. Cocaine-seeking is elicited by cocaine-associated cues, and the basolateral amygdala (BLA) and CeA are essential in forming and communicating drug-related associations that are thought to be critical in long-lasting relapse risk associated with drug addiction. Here we simulated a cue stimulus with high-frequency stimulation (HFS) of the BLA-CeA pathway to examine mechanisms that may contribute to drug-related associations.

Cocaine withdrawal enhances long-term potentiation induced by corticotropin-releasing factor at central amygdala glutamatergic synapses via CRF, NMDA receptors and PKA.

Cocaine addiction is an enduring, relapsing, behavioural disorder in which stressors reinstate cocaine-seeking even after prolonged abstinence. Evidence suggests that the 'anxiety-like' behaviour and stress associated with protracted withdrawal may be mediated by increased corticotropin-releasing factor (CRF) in the central nucleus of the amygdala (CeA), a part of the limbic circuitry engaged in the coding and transmission of stimulus-reward associations. In the present study we describe a long-lasting potentiation of glutamatergic transmission induced at lateral amygdala (LA)-to-CeA synapses by rat/human CRF.

Regulation of synaptic transmission by CRF receptors.

Corticotropin-releasing factor (CRF or CRH) and its family of related peptides have long been recognized as hypothalamic-pituitary-adrenal (HPA) axis peptides that function to regulate the release of other hormones, e.g., ACTH.

Fear learning induces persistent facilitation of amygdala synaptic transmission.

In the maintenance phase of fear memory, synaptic transmission is potentiated and the stimulus requirements and signalling mechanisms are altered for long-term potentiation (LTP) in the cortico-lateral amygdala (LA) pathway. These findings link amygdala synaptic plasticity to the coding of fear memories. Behavioural experiments suggest that the amygdala serves to store long-term fear memories.

A novel rat medial prefrontal cortical slice preparation to investigate synaptic transmission from amygdala to layer V prelimbic pyramidal neurons.

Electrophysiological recordings from identified synapses in CNS slice preparations in vitro provide important information regarding the connectivity of neuronal circuits and the underlying cellular mechanisms responsible for neuronal excitability and synaptic transmission. We present an anatomical, electrophysiological, and pharmacological characterization of a novel brain slice preparation (BLA-mPFC) to investigate basolateral amygdala synaptic input to rat layer V medial prefrontal cortex pyramidal neurons. A fluorescent tracer (DiI) unilaterally infused in vivo into the basolateral amygdala was used to detect amygdala efferent fibers innervating layer V of the prelimbic and infralimbic cortices within prefrontal cortex slices.

Chronic cocaine administration switches corticotropin-releasing factor2 receptor-mediated depression to facilitation of glutamatergic transmission in the lateral septum.

Corticotropin-releasing factor (CRF) and urocortin (Ucn I) are endogenous members among a family of CRF-related peptides that activate two different and synaptically localized G-protein-coupled receptors, CRF1 and CRF2. These peptides and their receptors have been implicated in stress responses and stress with cocaine abuse. In this study, we observed significant alterations in excitatory transmission and CRF-related peptide regulation of excitatory transmission in the lateral septum mediolateral nucleus (LSMLN) after chronic cocaine administration.

Two intra-amygdaloid pathways to the central amygdala exhibit different mechanisms of long-term potentiation.

Synaptic plasticity in the amygdala is thought to underlie aversive or rewarding learning and emotional memories. In this study, different mechanisms were found to underlie synaptic plasticity in lateral (LA) and basolateral (BLA) amygdala pathways to the primary output nucleus of the amygdala, the central amygdala (CeA). Specifically, 1) long-term potentiation (LTP) at the BLA-CeA synapses was independent of inhibition and mediated through N-methyl-d-aspartate receptors (NMDARs) and L-type voltage-gated calcium channels (VGCCs), and 2) LTP in the LA-CeA pathway was gated by inhibition and mediated through VGCCs but not NMDARs.

Internuclear synapse in the amygdala is not facilitated in fear conditioning.

The amygdala is essential for fear learning and memory. Synaptic transmission is enhanced in two pathways in the amygdala in fear conditioning. In this study we examined whether lateral (LA) to basolateral (BLA) amygdala synapses are potentiated and participate in intra-amygdala plasticity during the maintenance of fear memory.

Fear memories induce a switch in stimulus response and signaling mechanisms for long-term potentiation in the lateral amygdala.

Activity-dependent modification of synapses is fundamental for information storage in the brain and underlies behavioral learning. Fear conditioning is a model of emotional memory and anxiety that is expressed as an enduring increase in synaptic strength in the lateral amygdala (LA). Here we analysed synaptic plasticity in the rat cortico-LA pathway during maintenance of fear memory.

Corticotropin-releasing factor and Urocortin I modulate excitatory glutamatergic synaptic transmission.

Corticotropin-releasing factor (CRF)-related peptides serve as hormones and neuromodulators of the stress response and play a role in affective disorders. These peptides are known to alter complex behaviors and neuronal properties, but their receptor-mediated effects at CNS synapses are not well described. Here we show that excitatory glutamatergic transmission is modulated by two endogenous CRF-related peptide ligands, corticotropin-releasing factor [CRF rat/human (r/h)] and Urocortin I (Ucn I), within the central nucleus of the amygdala (CeA) and the lateral septum mediolateral nucleus (LSMLN).

NMDA currents and receptor protein are downregulated in the amygdala during maintenance of fear memory.

The amygdala plays a critical role in fear conditioning, a model of emotional learning and cue-induced anxiety. In the lateral amygdala, fear conditioning is associated with an enduring increase in synaptic strength mediated through AMPA receptors and with a reduction in paired-pulse facilitation, reflecting an increased probability of neurotransmitter release. Here we show that NMDA-mediated transmission in the thalamic-to-lateral amygdala pathway is not facilitated after fear conditioning, although probability of transmitter release is enhanced.

L-type voltage-gated calcium channels are involved in the in vivo and in vitro expression of fear conditioning.

Fear conditioning, a behavioral model of fear learning and cue-related anxiety, causes enhanced neuronal transmission in the thalamic to lateral amygdala pathway.(1,2) In the expression phase of learned fear, this increased transmission recorded in vitro is revealed in increased amplitudes of excitatory postsynaptic currents (EPSCs) and occlusion of paired-pulse facilitation (PPF) implicating a presynaptic increase in transmitter release. Here we examined the contribution of L-type calcium channels in fear conditioning.

Glucocorticoids alter calcium conductances and calcium channel subunit expression in basolateral amygdala neurons.

Glucocorticoid hormones, which are released in high amounts after stress, enter the brain where they bind to intracellular receptors that are abundant in limbic areas, in particular the hippocampus and amygdala nuclei. Behavioural studies indicate that glucocorticoids modulate learning and memory processes via receptors in the hippocampus and amygdala. So far, the effects of glucocorticoids on amygdala neurons have not been investigated at the cellular and molecular level.

Expression of fear-conditioning is accompanied by increased paired-pulse depression within the amygdala.

Fear-conditioning is a model of fear learning and anxiety. The lateral nucleus of the amygdala (LA) provides a critical link for relaying thalamic and cortical auditory information to the rest of the amygdala during the fear conditioning process. Alterations in excitatory synaptic transmission in the thalamic to LA pyramidal cells was studied using whole-cell patch clamp recordings in brain slices from fear-conditioned animals.