Biology subjects

Ecevitoglu, A.

Publications and source records attributed to Ecevitoglu, A..

3 recordsLinked to original sources

bioRxiv2026

Decoding instrumental lever pressing from prefrontal, accumbens, and hippocampal local field potentials: conservation across sex, task, and dopamine depletion

During operant behavior, oscillatory activity is coordinated across multiple brain regions and can change under different task conditions. In this study, we use a decoding approach to characterize these patterns and predict lever pressing behavior in rats from local field potentials (LFP) recorded bilaterally in the hippocampus, nucleus accumbens, and prefrontal cortex. We extract LFP features for band power and peak frequency and predict behavior across animals and conditions with a Poisson Generalized Linear Model (GLM). We use data from both male and female rats performing either fixed-ratio (FR40) or progressive (PROG) operant lever-pressing tasks, under vehicle (VEH) or tetrabenazine (TBZ), a vesicular monoamine transport (VMAT-2) inhibitor that depletes dopamine and induces depressive-like motivation dysfunction. We find that we can accurately predict lever pressing from multi-region LFP within-animals on a timescale of seconds with >30% variance explained. Although within-animal and within-condition predictions are highest, we also find, interestingly, that these decoders generalize across animals and across drug, sex, and task conditions, suggesting a stable association between LFP and behavior. We then evaluate whether LFP features can be used to decode long-term task variables, such as the number of presses since or until the next reinforcer. We find that LFP features can predict these long-term task variables, but that decoding relies on different LFP features for prediction than those used for immediate lever pressing. Altogether these results suggest that there are robust distributed patterns of LFP associated with lever-pressing behavior under multiple drug, task, and sex conditions.

neuroscience↗

bioRxiv2025

Effects of the Neutral CB1 Receptor Antagonist AM6527 on Spontaneous, Consummatory, and Motivated Behavior in Mice

RationaleThe cannabinoid type-1 receptor (CB1R) signaling pathway plays a central role in regulating motivational and feeding behaviors. Neutral CB1R antagonists represent a promising therapeutic class with potentially fewer adverse effects than inverse agonists, yet their behavioral effects remain incompletely characterized. ObjectivesWe investigated the behavioral profile of AM6527, orally bioavailable neutral CB1R antagonist, across naturalistic and operant paradigms in male mice. To evaluate dopaminergic involvement in AM6527s effects, we employed several pharmacological interventions. ResultsUsing machine learning-based Motion-Sequencing (MoSeq), which parses spontaneous behavior into sub-second syllables, we found that AM6527 did not affect overall speed in an open field, however, it increased the self-directed behaviors and reduced specific locomotor syllables at the highest dose tested. In a naturalistic reward consumption paradigm, AM6527 produced a dose-dependent reduction in milk intake. Operant conditioning paradigms revealed robust suppression of motivated responding on fixed ratio-3 and progressive ratio (PR) schedules for palatable milk reward, with the greatest impact on high-baseline performers under PR conditions. To understand the dopaminergic involvement, we co-administered dopaminergic drugs (targeting D1R, D2R, or dopamine transporter) which resulted in partial rescue of operant responding, indicating dopaminergic and non-dopaminergic contributions to AM6527s observed behavioral effects. ConclusionOur findings suggest that neutral CB1R antagonism suppresses consummatory and motivated behaviors via dopamine-dependent and -independent mechanisms. By leveraging sub-second behavioral analysis with MoSeq, we further reveal distinct changes in spontaneous behavior, underscoring the relevance of CB-based treatments for maladaptive appetitive and motivational states in both psychiatric and metabolic disorder.

neuroscience↗

bioRxiv2025

Autism-associated ASPM variant causes macrocephaly and social-cognitive deficits in mice

In autism spectrum disorder (ASD), a neurodevelopmental disorder with social-cognitive deficits, macrocephaly occurs in 20% of patients with severe symptoms. However, the role of macrocephaly in ASD pathogenesis remains unclear. Here, we address the mechanistic link between macrocephaly and ASD by investigating a novel ASD-associated gain-of-function A1877T mutation in ASPM (abnormal spindle-like microcephaly-associated). ASPM is a key regulator of cortical size and cell proliferation expressed in both excitatory and inhibitory neuronal progenitors but not in differentiated neurons. We found that Aspm gain-of-function knock-in mice exhibit macrocephaly, excessive embryonic neurogenesis with expanded outer radial glia, an increased excitatory-inhibitory (E-I) ratio, brain hyperconnectivity, and social-cognitive deficits with male specificity. Our results suggest that macrocephaly in ASD is not a proportional expansion of excitatory and inhibitory neurons, but a shift in the E-I ratio, independent of the expression patterns of the causative gene. Thus, macrocephaly alone can cause a subset of ASD-like symptoms.

neuroscience↗