Modulation of intrinsic excitability as a function of learning within the fear conditioning circuit

Abstract

Experience-dependent neuronal plasticity is a fundamental substrate of learning and memory. Intrinsic excitability is a form of neuronal plasticity that can be altered by learning and indicates the pattern of neuronal responding to external stimuli (e.g. a learning or synaptic event). Associative fear conditioning is one form of learning that alters intrinsic excitability, reflecting an experience-dependent change in neuronal function. After fear conditioning, intrinsic excitability changes are evident in brain regions that are a critical part of the fear circuit, including the amygdala, hippocampus, retrosplenial cortex, and prefrontal cortex. Some of these changes are transient and/or reversed by extinction as well as learning-specific (i.e. they are not observed in neurons from control animals). This review will explore how intrinsic neuronal excitability changes within brain structures that are critical for fear learning, and it will also discuss evidence promoting intrinsic excitability as a vital mechanism of associative fear memories. This work has raised interesting questions regarding the role of fear learning in changes of intrinsic excitability within specific subpopulations of neurons, including those that express immediate early genes and thus demonstrate experience-dependent activity, as well as in neurons classified as having a specific firing type (e.g. burst-spiking vs. regular-spiking). These findings have interesting implications for how intrinsic excitability can serve as a neural substrate of learning and memory, and suggest that intrinsic plasticity within specific subpopulations of neurons may promote consolidation of the memory trace in a flexible and efficient manner.

Neural responses to negative facial emotions: Sex differences in the correlates of individual anger and fear traits

“…Along with the amygdala, hippocampus and prefrontal cortex, the RSC, posterior cingulate cortex (PCC) and precuneus (PCu) have been implicated in emotional (particularly fear) learning and memory in both preclinical ( Todd et al, 2019 ; Vogt, 2019 ; Yousuf et al, 2020 ) and clinical ( Holschneider et al, 2014 ; Kveraga et al, 2015 ; Van den Stock et al, 2014 ; Zhan et al, 2018 ) studies. For instance, fear induction with exposure to video clips elicited higher activity in bilateral anterior insula and right hemispheric parahippocampal gyrus (PHG), PCC, and PCu ( Zhan et al, 2018 ).…”

Persistently increased post-stress activity of paraventricular thalamic neurons is essential for the emergence of stress-induced maladaptive behavior

“…Mechanisms of persistent activity in the fear circuit are intensively studied 64 . Understanding the cellular bases of the post-stress shift in PVT/CR+ activity requires further investigation.…”

Intrinsic Excitability in Layer IV–VI Anterior Insula to Basolateral Amygdala Projection Neurons Correlates with the Confidence of Taste Valence Encoding

“…5 ). We focused on BS LIV–VI aIC-BLA projecting neurons since bursting has been implicated in coincidence detection by deep-layer neurons ( Boudewijns et al, 2013 ; Shai et al, 2015 ), as well as the encoding of novelty and valence relating to different modalities ( Song et al, 2015 ; Dunn et al, 2018 ; Yousuf et al, 2019 ). Our PCA of intrinsic properties in BS LVI-VI aIC-BLA projecting neurons demonstrated that distinct plasticity rules are at play depending on the balance between the probability for associative learning and the certainty with which taste predicts the valence of experience during retrieval (Extended Data Figs.…”