Biology subjects

Schamiloglu, S.

Publications and source records attributed to Schamiloglu, S..

3 recordsLinked to original sources

bioRxiv2026

Synaptic dynamics as a tunable substrate shaping neuronal activity sequences

A central tenet of cerebellar computation posits that granule cells generate sparse spatiotemporal activity patterns that support precisely timed motor and cognitive outputs. Using high-speed in vivo calcium and glutamate imaging combined with slice electrophysiology, we show that heterogeneous synaptic dynamics transform mossy fiber inputs into temporally sparse, sequential patterns of GC activity. Region-specific differences in MF glutamate release shape GC response duration and sparsity, tuning the temporal statistics of population sequences to match sensorimotor associative learning demands. These findings provide direct evidence for temporally sparse GC sequences and establish synaptic dynamics as a ubiquitous, tunable mechanism structuring neural activity in time.

neuroscience↗

bioRxiv2022

Arrestin-3 agonism at D3 dopamine receptors defines a subclass of second generation antipsychotics that promotes drug tolerance

Second generation antipsychotics (SGAs) are front-line treatments for serious mental illness. Often, individual patients benefit only from some SGAs and not others. The mechanisms underlying this unpredictability in treatment efficacy remain unclear. All SGAs bind the D3 dopamine receptor (D3R) and are traditionally considered antagonists for dopamine receptor signaling. Here, we report that some clinically important SGAs function as arrestin-3 agonists at D3R, resulting in modulation of calcium channels localized to the site of action potential initiation in prefrontal cortex pyramidal neurons. We further show that chronic treatment with an arrestin-3 agonist-SGA, but not an antagonist-SGA, abolishes D3R function through post-endocytic receptor degradation by G-protein coupled receptor-associated sorting protein-1 (GASP1). These results implicate D3R-arrestin-3 signaling as a source of SGA variability, highlighting the importance of including arrestin-3 signaling in characterizations of drug action. Furthermore, they suggest that post-endocytic receptor trafficking that occurs during chronic SGA treatment may contribute to treatment efficacy.

neuroscience↗

bioRxiv2021

Top-down control of hippocampal signal-to-noise by prefrontal long-range inhibition

The prefrontal cortex (PFC) is postulated to exert top-down control by modulating information processing throughout the brain to promote specific actions based on current goals. However, the pathways mediating top-down control remain poorly understood. In particular, knowledge about direct prefrontal connections that might facilitate top-down prefrontal control of information processing in the hippocampus remains sparse. Here we describe novel monosynaptic long-range GABAergic projections from PFC to hippocampus. These preferentially inhibit vasoactive intestinal polypeptide expressing interneurons, which are known to disinhibit hippocampal microcircuits. Indeed, stimulating prefrontal-hippocampal GABAergic projections increases hippocampal feedforward inhibition and reduces hippocampal activity in vivo. The net effect of these actions is to specifically enhance the signal-to-noise ratio for hippocampal representations of objects. Correspondingly, stimulation of PFC-to-hippocampus GABAergic projections promotes object exploration. Together, these results elucidate a novel top-down pathway in which long-range GABAergic projections target disinhibitory microcircuits, thereby enhancing signals and network dynamics underlying exploratory behavior.

neuroscience↗