Topic: fear memory

Circuit Mechanisms of Remote Memory

Memories of emotionally-salient events are long-lasting, guiding behavior from minutes to years after learning. The prelimbic cortex (PL) is required for fear memory retrieval across time and is densely interconnected with many subcortical and cortical areas involved in recent and remote memory recall, including the temporal association area (TeA). While the behavioral expression of a memory may remain constant over time, the neural activity mediating memory-guided behavior is dynamic. In PL, different neurons underlie recent and remote memory retrieval and remote memory-encoding neurons have preferential functional connectivity with cortical association areas, including TeA. TeA plays a preferential role in remote compared to recent memory retrieval, yet how TeA circuits drive remote memory retrieval remains poorly understood. Here we used a combination of activity-dependent neuronal tagging, viral circuit mapping and miniscope imaging to investigate the role of the PL-TeA circuit in fear memory retrieval across time in mice. We show that PL memory ensembles recruit PL-TeA neurons across time, and that PL-TeA neurons have enhanced encoding of salient cues and behaviors at remote timepoints. This recruitment depends upon ongoing synaptic activity in the learning-activated PL ensemble. Our results reveal a novel circuit encoding remote memory and provide insight into the principles of memory circuit reorganization across time.

Consolidation of remote contextual memory in the neocortical memory engram

Recent studies identified memory engram neurons, a neuronal population that is recruited by initial learning and is reactivated during memory recall.  Memory engram neurons are connected to one another through memory engram synapses in a distributed network of brain areas.  Our central hypothesis is that an associative memory is encoded and consolidated by selective strengthening of engram synapses.  We are testing this hypothesis, using a combination of engram cell labeling, optogenetic/chemogenetic, electrophysiological, and virus tracing approaches in rodent models of contextual fear conditioning.  In this talk, I will discuss our findings on how synaptic plasticity in memory engram synapses contributes to the acquisition and consolidation of contextual fear memory in a distributed network of the amygdala, hippocampus, and neocortex.

Drifting assemblies for persistent memory: Neuron transitions and unsupervised compensation

Change is ubiquitous in living beings. In particular, the connectome and neural representations can change. Nevertheless behaviors and memories often persist over long times. In a standard model, associative memories are represented by assemblies of strongly interconnected neurons. For faithful storage these assemblies are assumed to consist of the same neurons over time. We propose a contrasting memory model with complete temporal remodeling of assemblies, based on experimentally observed changes of synapses and neural representations. The assemblies drift freely as noisy autonomous network activity or spontaneous synaptic turnover induce neuron exchange. The exchange can be described analytically by reduced, random walk models derived from spiking neural network dynamics or from first principles. The gradual exchange allows activity-dependent and homeostatic plasticity to conserve the representational structure and keep inputs, outputs and assemblies consistent. This leads to persistent memory. Our findings explain recent experimental results on temporal evolution of fear memory representations and suggest that memory systems need to be understood in their completeness as individual parts may constantly change.

The activity of phosphodiesterase 4 in the dorsal hippocampus during reconsolidation sustains fear memory over time

Acute insulin administration enhances contextual fear memory independently of adrenaline, through increased hippocampus Bdnf expression

Brain-wide epigenetics mapping of fear memory engram cells

A fear memory engram in the mouse auditory cortex

A midbrain-extended amygdala pathway controls contextual fear memory and predator odor avoidance

Neuropeptidergic modulation of cortical circuits for fear memory

Role of hippocampo-prefrontal circuits in fear memory consolidation

The Temporal Study of Traumatic Stress Related Fear Memory Retrieval in a Rat Model of Post-Traumatic Stress Disorder: Brain Wave and Transcriptome-Level Gene Profiling