Inhibitory engrams in perception and memory

Abstract

Nervous systems use excitatory cell assemblies to encode and represent sensory percepts. Similarly, synaptically connected cell assemblies or "engrams" are thought to represent memories of past experience. Multiple lines of recent evidence indicate that brain systems create and use inhibitory replicas of excitatory representations for important cognitive functions. Such matched "inhibitory engrams" can form through homeostatic potentiation of inhibition onto postsynaptic cells that show increased levels of excitation. Inhibitory engrams can reduce behavioral responses to familiar stimuli, thereby resulting in behavioral habituation. In addition, by preventing inappropriate activation of excitatory memory engrams, inhibitory engrams can make memories quiescent, stored in a latent form that is available for contextrelevant activation. In neural networks with balanced excitatory and inhibitory engrams, the release of innate responses and recall of associative memories can occur through focused disinhibition. Understanding mechanisms that regulate the formation and expression of inhibitory engrams in vivo may help not only to explain key features of cognition but also to provide insight into transdiagnostic traits associated with psychiatric conditions such as autism, schizophrenia, and posttraumatic stress disorder.Percepts are thought to be represented in the brain by excitatory activity in groups of neurons, described as cell assemblies (1). Memories may similarly be represented by excitatory connections across different cell assemblies, which form when experiences trigger coordinated activity. Several recent studies indicate that the storage and reactivation of these excitatory "engrams" (2), respectively, may be accompanied by creation and modulation of matched inhibitory engrams. Here, we propose that inhibitory engrams, also termed "negative images" or "inhibitory representations," explain two fundamental features of animal and human psychology: first, behavioral habituation, which allows organisms to ignore familiar, frequently encountered percepts or stimuli, and, second, latent memory, wherein the brain stores tens of thousands of memories in a silent or latent state until recall is required. Such inhibitory engrams can be constructed in neural networks through simple, evolutionarily primitive, synaptic and cellular mechanisms, which are recognized to be involved in the phenomenon of excitatory-inhibitory (EI) balance observed across the brain.Neurons and neural circuits normally operate within a preset range of activity. Outside this range, altered levels of neuronal spiking trigger a variety of homeostatic mechanisms ranging from compensatory ion channel expression to local synaptic scaling (3, 4). These homeostatic mechanisms ensure that the activity parameters of a neuron operate around a set point such that the spiking rates remain stable and a balance of depolarizing and hyperpolarizing currents is maintained. As a consequence, excitation and inhibition are both locally and globally balanced, despite...

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