Biology subjects

Davatolhagh, M. F.

Publications and source records attributed to Davatolhagh, M. F..

5 recordsLinked to original sources

bioRxiv2026

Comprehensive 3D mapping reveals distinct spatial gradients of SST, PV, and TH interneurons across the mouse caudoputamen

In addition to spatially organized excitatory forebrain inputs along its mediolateral, dorsoventral, and anteroposterior axes, the striatum relies on cellular diversity to subserve its myriad processing functions. Distinct striatal GABAergic interneuron subtypes, including somatostatin (SST), parvalbumin (PV), and tyrosine hydroxylase (TH) interneurons likely subserve complementary computational roles. However, a detailed understanding of how these microcircuit components are distributed across striatal territories remains lacking. To address this gap, we generated a comprehensive three-dimensional atlas of SST, PV, and TH interneurons across the mouse caudoputamen using genetic labeling, brain-wide imaging, and voxel-wise quantification. We found that SST and TH interneurons were relatively enriched in the ventral caudoputamen, whereas PV interneurons were enriched dorsally. In addition, PV and TH interneurons exhibited opposing anteroposterior distribution patterns, with PV interneurons enriched posteriorly and TH interneurons showing a marked decline in density towards the striatal tail. Consequently, while the three interneuron subtypes displayed comparable densities in the functionally defined lateral striatum and anterior ventromedial striatum, PV interneurons predominated in the dorsomedial striatum and tail of striatum. We did not observe major sex differences. Together, these findings reinforce the view that the striatum is not a monolithic structure: in addition to structured excitatory inputs, inhibitory microcircuits themselves are differentially distributed across striatal territories, providing region-specific constraints on circuit computation. By integrating interneuron organization into existing anatomical frameworks, this atlas provides a foundation for linking striatal anatomy to function across behavioral domains.

neuroscience↗

bioRxiv2025

Altered Use of Prior Expectations and Modified Neural Dynamics in a Mouse Model of Autism

In dynamic environments, updating beliefs based on past experiences (priors) is essential for optimal decision-making. Prior utilization is often impaired in psychiatric disorders, affecting perception and behavior. We investigate how Neurexin1 (Nrxn1 ) loss-of-function disrupts this process, providing insight into circuit deficits underlying sensorimotor dysfunction. While the synaptic role of Nrxn1 role is well studied, its impact on network dynamics and decision-making behavior remain unclear. Using widefield calcium imaging, we assess cortex-wide activity in mice performing a two-choice task to probe how priors influence visually-guided decisions. This task requires the mouse to combine sensory evidence with the prior probability over the stimulus side. We find Nrxn1 KO mice underutilized priors and were slower to update choices based on feedback. During decision-making, cortex-wide cortical activity is both elevated and increasingly correlated in Nrxn1 KO mice, independent of task period. Moreover, a larger fraction of cortical variance was explained by movement variables, consistent with stronger coupling of cortical activity to motor signals and a bias toward movement-related dynamics. These findings suggest that core computations underlying decision-making, such as integrating past experience with current evidence, depend on intact synaptic mechanisms shaped by genes like Nrxn1.

neuroscience↗

bioRxiv2022

Reproducibility of in-vivo electrophysiological measurements in mice

Understanding brain function relies on the collective work of many labs generating reproducible results. However, reproducibility has not been systematically assessed within the context of electrophysiological recordings during cognitive behaviors. To address this, we formed a multi-lab collaboration using a shared, open-source behavioral task and experimental apparatus. Experimenters in ten laboratories repeatedly targeted Neuropixels probes to the same location (spanning secondary visual areas, hippocampus, and thalamus) in mice making decisions; this generated a total of 121 experimental replicates, a unique dataset for evaluating reproducibility of electrophysiology experiments. Despite standardizing both behavioral and electrophysiological procedures, some experimental outcomes were highly variable. A closer analysis uncovered that variability in electrode targeting hindered reproducibility, as did the limited statistical power of some routinely used electrophysiological analyses, such as single-neuron tests of modulation by individual task parameters. Reproducibility was enhanced by histological and electrophysiological quality-control criteria. Our observations suggest that data from systems neuroscience is vulnerable to a lack of reproducibility, but that across-lab standardization, including metrics we propose, can serve to mitigate this.

neuroscience↗

bioRxiv2020

Striatal low-threshold spiking interneurons locally gate dopamine during learning

Low-threshold spiking interneurons (LTSIs) in the dorsomedial striatum are potent modulators of goal-directed learning. Here, we uncover a novel function for LTSIs in locally and directly gating striatal dopamine, using in vitro fast scan cyclic voltammetry as well as in vivo GRAB-DA sensor imaging and pharmacology during operant learning. We demonstrate that LTSIs, acting via GABAB signaling, attenuate dopamine release, thereby serving as local coordinators of striatal plasticity.

neuroscience↗

bioRxiv2020

Neurexin1α differentially regulates synaptic efficacy within striatal circuits

Mutations in genes essential for shared aspects of synaptic function throughout the CNS, such as the presynaptic adhesion molecule Neurexin1 (Nrxn1), are strongly implicated in neuropsychiatric pathophysiology. As the input nucleus of the basal ganglia, the striatum integrates diverse excitatory projections governing cognitive and motor control, and its functional impairment underlies neuropsychiatric disorders. While prior work has emphasized Neurexins contributions to synaptic transmission in hippocampus and brainstem, their function in striatal circuits remains unstudied. As Nrxn1 is highly expressed at striatal inputs, we employed optogenetic-mediated afferent recruitment of dorsal prefrontal cortex-dorsomedial striatal (DMS) connections, uncovering a decrease in net synaptic strength specifically onto indirect pathway spiny neurons in both Nrxn1+/- and Nrxn1-/- mice, driven by reductions in transmitter release probability. In contrast, thalamic excitatory inputs to DMS demonstrated relatively normal excitatory synaptic strength. These findings suggest that dysregulation of Nrxn1 modulates striatal function in an input and target-specific manner.

neuroscience↗