Biology subjects

Timplalexi, M.

Publications and source records attributed to Timplalexi, M..

3 recordsLinked to original sources

bioRxiv2025

Feedforward and feedback population dynamics during binocular conflict in mouse visual cortex

Binocular rivalry arises when incongruent images are presented to the two eyes, producing stochastic alternations in perceptual dominance. While rivalry has been extensively studied in species with highly developed binocular vision, it is unclear whether similar representational dynamics occur in the mouse, a model system that allows large-scale cellular and circuit-level measurements. Here we used two-photon calcium imaging in awake mice to examine the population dynamics of primary visual cortex (V1) and long-range feedback axons from retrosplenial cortex (RSC) during presentation of dichoptically incongruent drifting gratings and natural movies. At the single-cell level, incongruent stimulation increased trial-to-trial variability of visually evoked responses relative to monocular stimulation. Linear SVM decoders trained on monocular responses revealed that during prolonged incongruent stimulation, V1 population activity alternated stochastically between representations of the two competing stimuli in a contrast-dependent manner. Decoder confidence was independent of pupil-indexed arousal state suggesting the dynamics observed may depend mostly on feedforward mechanisms. Transition analyses showed that switches in decoder output were typically driven by the emergence of responses to the ipsilateral stimulus, consistent with release from suppression of the non-dominant population. During incongruent presentation of natural movies, similar representational alternations were observed, indicating that rivalry-like dynamics were not dependent on orientation-selective adaptation. Imaging of RSC[->]V1 feedback axons revealed retinotopically specific, eye and orientation-selective signals that also alternated in dominance across time. These results establish the mouse as a model of rivalry-like cortical dynamics, demonstrate that both feedforward and feedback circuits contribute to representational alternation during binocular conflict, and provide a framework for mechanistic dissection of bistable perception.

neuroscience↗

bioRxiv2025

The functional organization of retrosplenial feedback to V1

Cortical feedback from higher frontal and association areas to early sensory cortex is thought to contribute to a range of cognitive processes in which sensory signals are processed in a context sensitive manner. Despite the ubiquity of feedback circuitry in the cortex, the information carried by feedback connections, and the principles governing how it is targeted from area to area remains poorly understood. Here we characterized the functional properties of a prominent feedback circuit which links retrosplenial cortex (RSC) and primary visual cortex (V1). We found that RSC[->]V1 axons relay retinotopically selective signals to V1 which at a coarse scale match the region of the V1 retinotopic map innervated, were tuned for spatial and temporal frequency, but not tuned for orientation. Two-color imaging of RSC[->]V1 boutons and local L2/3 V1 neurons further revealed that at a finer scale RSC[->]V1 bouton receptive fields are systematically offset relative to those of V1 in the nasal direction, consistent with RSC[->]V1 boutons conveying signals predictive of upcoming V1 activity in the retinotopic region innervated during forward movement.

neuroscience↗

bioRxiv2021

Phencyclidine-induced psychosis causes hypersynchronization and disruption of connectivity within prefrontal-hippocampal circuits that is rescued by antipsychotic drugs

Neural synchrony and functional connectivity are disrupted in neuropsychiatric disorders such as schizophrenia. However, these alterations and how they are affected by commonly prescribed neuropsychiatric medication have not been characterized in depth. Here, we investigated changes in neural dynamics of circuits involving the prefrontal cortex and the hippocampus during psychosis induced by the NMDAR antagonist phencyclidine and subsequent recovery by three different antipsychotic drugs (APDs), the classical APD haloperidol and two atypical APDs, clozapine and risperidone, in freely moving mice. We found that the psychotomimetic effects of phencyclidine were associated with hypersynchronization and disrupted communication of prefrontal-hippocampal pathways. Major alterations occurred in the prefrontal cortex, where phencyclidine increased oscillatory power at delta, high gamma and high frequencies (<100 Hz) and generated aberrant cross-frequency coupling, suggesting the presence of hypersynchronous cortical microcircuits. Cross-regional coupling and phase coherence were also enhanced, further reflecting that the circuits functional connectivity was increased. Phencyclidine also redirected the intrinsic flow of information at theta frequencies that traveled from the hippocampus to the prefrontal cortex into delta rhythms that traveled in the opposite direction. The three APDs rescued most phencyclidine-induced changes in power, coupling, phase coherence, and directionality, suggesting common cellular mechanisms of antipsychotic action. However, some differential effects were identified, likely resulting from the distinct affinity the three APDs have for dopamine and serotonin receptors. We therefore investigated how serotonin 1A (5-HT1AR) and 2A receptors (5-HT2AR) compare to the actions of the APDs. 5-HT2AR antagonism by M100907 and 5-HT1AR agonism by 8-OH-DPAT rescued phencyclidine-induced increased power, coupling and phase coherence but were unable to normalize the circuits theta directionality. This suggests that other targets of the AAPDs working in tandem with 5-HT1ARs and 5-HT2ARs are required to ameliorate this key feature of the circuit.

neuroscience↗