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In cortical circuits, memory engrams emerge as distributed patterns of activity across ensembles of neurons. Inhibitory interneurons, once considered passive regulators of network excitability, are now recognized as active sculptors of these patterns. Through synaptic plasticity, interneurons modulate the timing and precision of excitatory bursts, creating windows during which synapses strengthen or weaken in a lineage of activity that encodes a memory. This dynamic is achieved via multiple interneuron subtypes, each with distinct connectivity and signaling profiles. By shaping oscillations, synchronization, and the flow of information, inhibitory cells help define which neurons participate in an engram and how robustly they participate under varying contexts and demands.

The plasticity of inhibitory circuits operates on several scales, from short-term modulation to long-term structural changes. At fast timescales, interneurons can alter the gain and rhythmicity of excitatory inputs through mechanisms like dynamic inhibitory postsynaptic currents and feedforward inhibition. Over longer periods, activity-dependent plasticity at inhibitory synapses changes how readily a neuron can be recruited into a memory trace. This long-range remodeling can stabilize a memory by preventing runaway excitation and by maintaining an optimal balance that preserves the fidelity of recall. The interplay between fast and slow processes ensures memory traces remain interpretable across behaviorally relevant timescales and environmental changes.

A key concept in memory science is that engrams are not static clusters but evolving networks. Inhibitory plasticity participates in this evolution by refining which neurons participate as the representation of an experience grows. When a salient event occurs, inhibitory synapses may weaken onto specific excitatory connections, allowing those connections to strengthen through Hebbian-like mechanisms. Conversely, other inhibitory pathways may strengthen to dampen competing representations, sharpening the focus of the memory. This selective modulation helps ensure that a memory trace remains distinct from nearby experiences, reducing interference and supporting more reliable recall under noisy or overlapping sensory input.

Cortical inhibitory interneurons contribute to timing precision, a critical element of memory encoding. Gamma oscillations, often generated by the coordinated activity of inhibitory networks, coordinate the temporal structure of spikes across ensembles. Plastic changes in inhibitory synapses can adjust the frequency and coherence of these oscillations, thereby aligning synaptic changes with relevant behavioral events. This temporal alignment ensures that synaptic strengthening occurs during meaningful activity windows, reinforcing the correct associations and preventing maladaptive remodeling. The net effect is a more coherent, retrievable memory signal that persists despite fluctuations in attention or context.

Consolidation is a period when memories become more durable through repeated reactivation and structural changes. Inhibitory interneurons help regulate the reactivation timing across cortical areas, ensuring replay episodes reinforce the appropriate synapses without amplifying noise. Plasticity at inhibitory synapses can either gate or gate-break these replay events, controlling which excitatory connections are strengthened during each iteration. Such control reduces the likelihood of eroding the original memory with time or with new conflicting experiences. By preserving a stable backbone of the engram, inhibitory plasticity supports long-term retention while still allowing adaptive updating when necessary.

Beyond individual synapses, interneuron networks participate in circuit motifs that contribute to memory resilience. Feedforward and feedback inhibitory pathways create loops that constrain runaway excitation and promote sparsity in coding. Plastic changes within these motifs can adjust the thresholds for recruiting neurons into the engram, thereby influencing how easily memories can be reactivated. This gating mechanism is essential for striking a balance between recall stability and flexibility, enabling memories to survive aging, stress, and shifts in sensory environments.

Parvalbumin-expressing interneurons are often implicated in fast, precise inhibitory control that supports sharp temporal discrimination. Their plasticity tends to modulate the synchronization of excitatory populations, which is crucial during initial memory formation. When these interneurons adapt their inhibitory outputs in response to experience, they help distribute plastic changes across the network in a controlled fashion. This can prevent excessive clustering of activity and maintain a distributed representation that is easier to retrieve. The result is a memory trace that remains legible across different states of arousal and attention.

Somatostatin-containing interneurons provide dendritic targeting that shapes how inputs at distal sites influence engram formation. By adjusting dendritic inhibitory tone through experience-driven plasticity, these cells regulate how sensory and contextual information is integrated during learning. Such modulation affects the eligibility of specific synapses for plastic change, biasing which inputs contribute most to the evolving memory. Consequently, somatostatin interneurons contribute to robust, context-sensitive memories that adapt to new information without losing core content.

Vasoactive intestinal peptide (VIP) interneurons often orchestrate disinhibitory circuits that transiently release principal neurons from inhibition. This dynamic control can create permissive windows for plasticity to occur at excitatory synapses during learning. The plasticity of these VIP circuits, modulated by behavioral state and neuromodulators, helps synchronize memory formation with motivational relevance. Through these mechanisms, cortical networks can enhance encoding efficiency when a memory is behaviorally important, while preventing unnecessary changes when the stimuli are inconsequential.

Interneurons also contribute to the spatial structure of memory engrams. By shaping the microcircuit microdomains where activity concentrates during learning, inhibitory plasticity helps establish topographic maps of memory representation. Changes in inhibitory tone across cortical layers influence how local ensembles interact, promoting coherent ensemble assembly and limiting fragmentation of the engram. The evolving topology of these microdomains supports integration of new experiences with previously stored information, yielding memories that are both cohesive and adaptable.

Traditional models often emphasize excitatory synaptic changes as the primary substrate of memory. Contemporary views acknowledge that inhibitory plasticity is equally essential, providing stability and regulation. By controlling excitability, timing, and connectivity, inhibitory interneurons sculpt not only how memories are formed but how they endure. This perspective highlights the need for examining inhibitory pathways in isolation and within broader networks. Understanding their plasticity provides insight into resilience against interference, gradual forgetting, and recovery after disruption, ultimately refining our grasp of cortical memory architecture.

Investigations combining in vivo imaging, electrophysiology, and computational modeling reveal the multifaceted roles of inhibitory plasticity in engram dynamics. Researchers are mapping how specific interneuron subtypes contribute to recall fidelity, interference resistance, and update flexibility. As these studies progress, the field moves toward integrative frameworks that explain how inhibitory changes interact with neuromodulatory states to maintain memory integrity. The emerging picture is one where inhibition is not a mere counterbalance but a central determinant of how memories are encoded, stabilized, and retrieved across time and experience.