Neurons Specifically Activated by Fear Learning in Lateral Amygdala Display Increased Synaptic Strength

Abstract

The lateral amygdala (LA) plays a critical role in the formation of fear-conditioned associative memories. Previous studies have used c-fos regulated expression to identify a spatially restricted population of neurons within the LA that is specifically activated by fear learning. These neurons are likely to be a part of a memory engram, but, to date, functional evidence for this has been lacking. We show that neurons within a spatially restricted region of the LA had an increase in both the frequency and amplitude of spontaneous postsynaptic currents (sPSC) when compared to neurons recorded from home cage control mice. We then more specifically addressed if this increased synaptic activity was limited to learning-activated neurons. Using a fos-tau-LacZ (FTL) transgenic mouse line, we developed a fluorescence-based method of identifying and recording from neurons activated by fear learning (FTL+) in acute brain slices. An increase in frequency and amplitude of sPSCs was observed in FTL+ neurons when compared to nonactivated FTL− neurons in fear-conditioned mice. No learning-induced changes were observed in the action potential (AP) input-output relationships. These findings support the idea that a discrete LA neuron population forms part of a memory engram through changes in synaptic connectivity.

Interaction of Fear Conditioning with Eyeblink Conditioning Supports the Sensory Gating Hypothesis of the Amygdala in Men

“…The amygdala is critically involved in acquisition and retention of learned fear responses (Weisz et al, 1992;Rogan et al, 1997;Rosenkranz et al, 2003;Schroeder and Shinnick-Gallagher, 2005;Butler et al, 2018). Extinction of learned fear requires inhibition of the amygdala (Amano et al, 2010;Herry et al, 2010;Krabbe et al, 2018).…”

An update on memory formation and retrieval: An engram‐centric approach

“…We re‐created this figure according to the data presented in Tonegawa et al. 2015 48 and updated by adding following engram locations: 49–51 …”

The Synaptic Theory of Memory: A Historical Survey and Reconciliation of Recent Opposition

“…Specifically, when a strong stimulus occurs in the external environment, it drives high frequency stimulus trains (tetanic activity) in the neurons of a particular cell assembly, which, through their simultaneous synaptic activity, represent particular elements of the external stimulus (Buzsáki, 2010 ). Such a cell assembly or neural network has been identified for fear memory (Butler et al, 2015 , 2018 ).…”

“…Many of these cell assemblies firing consecutively form a phase sequence which connects the individual elements to produce a more complete mental representation, or train of thought (Almeida-Filho et al, 2014 ). Once the synaptic connections in the cell assemblies forming a phase sequence are modified by experience, subsequent activation of this specific array of neurons results in the experiential recollection of the memory stored in the constellation of modified synaptic connections (Nabavi et al, 2014 ; Josselyn et al, 2015 ; Butler et al, 2018 ).…”

“…Hebb ( 1949 ; page 129) suggested that once a memory phase sequence has been formed from a set of cell assemblies, it becomes independent of any particular sensory stimulation; thus, a memory formed from visual stimuli may be activated by tactile or auditory stimuli. Experimental evidence shows that the synaptic weights of a predictable set of synapses are altered during learning and these modifications in synaptic weight are part of the processes underlying learning (Butler et al, 2015 , 2018 ). Yet, subsequent destruction of the modified synapse rarely eliminates learning (Takeuchi et al, 2014 ; Trettenbrein, 2016 ).…”