Biology subjects

Hagopian, L. L.

Publications and source records attributed to Hagopian, L. L..

4 recordsLinked to original sources

bioRxiv2026

Smells like γ-synchrony: Insula-prefrontal communication depends on γ-synchrony and supports modality-specific changes in behavioral strategies

The prefrontal cortex is critical for many aspects of flexible behavior, but how it interacts with other brain regions to perform this function remains largely unknown. The insula is bidirectionally coupled with prefrontal cortex and known to be necessary for many aspects of cognition. Here we examined how the medial insular cortex (mIC) and medial prefrontal cortex (mPFC) interact to promote flexible behavior. Disrupting mIC-mPFC connectivity interferes with the ability of mice to learn shifts from texture cue-based behavioral strategies to odor-based ones (but not vice-versa). Using genetically encoded voltage indicators, we find a corresponding increase of in-phase gamma-frequency synchronization between mIC and mPFC parvalbumin-expressing inhibitory neurons during texture-to-odor shifts. Finally, we confirmed that optogenetically perturbing this synchronization disrupts texture-to-odor (but not odor-to-texture) shifts. These results establish a critical role for gamma synchronization in insula-prefrontal communication, and show that this communication plays a sensory modality-specific role in flexible behavior.

neuroscience↗

bioRxiv2026

NPAS4 refines spatial and temporal firing in CA1 pyramidal neurons

NPAS4 is an activity-dependent transcription factor that, in CA1 of the hippocampus, regulates inhibitory synapses made onto the active pyramidal neuron. In principle, NPAS4 thereby allows the past activity of a neuron to influence how it encodes information, although this has not yet been demonstrated. Here, we generated a sparse, CA1-specific knockout (KO) of NPAS4 in the mouse hippocampus and used optogenetic tagging to identify KO neurons in vivo. Recordings from intermingled wild-type (WT) and KO neurons in awake behaving animals revealed that NPAS4 deletion degrades spatial representations and temporal precision of spiking: KO neurons exhibited larger place fields with reduced in-field firing and increased out-of-field firing, less stable place fields, reduced coupling to local field potential theta oscillations, and diminished phase precession. These findings demonstrate that NPAS4 plays a crucial role in refining the spatial and temporal properties of CA1 pyramidal neuron spikes, which themselves are thought to be fundamental building blocks of more complex processes such as learning and memory.

neuroscience↗

bioRxiv2025

Synaptic plasticity of prefrontal long-range inhibition regulates cognitive flexibility

While glutamatergic synaptic plasticity is believed to be a fundamental mechanism mediating learning, the behavioral significance of plasticity at cortical GABAergic synapses remains less well understood. Furthermore, despite recent discoveries of long-range projections from neocortical GABAergic neurons, details about how they function are also sparse. Here we combine behavioral optogenetics with patch-clamp electrophysiology to link plasticity at long-range GABAergic synapses with higher-order cognitive functions. Specifically, learning extradimensional rule shifts potentiates callosal GABAergic synapses from prefrontal parvalbumin-expressing (PV) neurons onto corticothalamic neurons. Disrupting this potentiation by inhibiting callosal PV terminals during rule shifts induces perseveration, whereas reinstating this potentiation with subsequent gamma-frequency callosal PV terminal stimulation restores flexible behavior. This shows how a novel plasticity locus can regulate brain circuits underlying normal cognition and pathological states.

neuroscience↗

bioRxiv2024

Cell type-specific dynamics of prefrontal gamma synchrony during flexible behavior

Cognitive dysfunction in conditions such as schizophrenia involves disrupted communication between the prefrontal cortex (PFC) and mediodorsal thalamus (MD). Parvalbumin interneurons (PVI) are known to regulate PFC microcircuits and generate gamma-frequency ([~]40Hz) oscillations - fast, synchronized neural rhythms that are recruited during many executive functions, necessary for cognitive flexibility, and deficient in schizophrenia. While targeting PVI-mediated gamma oscillations holds great therapeutic promise, their nature and specific functions, e.g., for regulating PFC[->]MD communication, remain elusive. Using dual-color voltage indicators and optogenetics, we reveal that PVIs dynamically entrain MD-projecting PFC neurons both locally and contralaterally, giving rise to multiple distinct circuit-specific patterns of distributed synchronization that are recruited in a behaviorally-specific manner to support particular aspects of flexible behavior. Thus, gamma oscillations are not unitary phenomena characterized by one microcircuit-wide pattern of entrainment. Rather, they comprise diverse motifs, defined by specific cell types and phase relationships, that are dynamically recruited for specific functions.

neuroscience↗