Biology subjects

Muniak, M. A.

Publications and source records attributed to Muniak, M. A..

4 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

Neuronal architecture of the mouse insular cortex underlying its diverse functions

The insular cortex integrates interoceptive and exteroceptive information to mediate bodily homeostasis, emotion, learning, and potentially consciousness.1-4 However, the cellular and circuit substrates governing the insula and other associative cortices are poorly understood compared to primary cortices. Here, we quantify the dendritic morphology together with electrical properties, local inputs, and/or projections of 1,093 insular pyramidal neurons. These neurons are mapped onto a quantitative anatomical model of the insula based on a Nissl-staining coordinate framework. Using improved algorithms, we define 21 morphological, 12 electrical, and 9 input neuronal types, and identify several morphological and input types that are unique to the insula. Further, we find that morphological properties constrain and often predict inputs, electrical properties, or projection targets. Several morphological types are differentially distributed between the functionally distinct anterior and posterior insula, providing the substrates for a quantitative demarcation between the anterior and posterior insular subregions. Surprisingly, certain neuronal types receive intra-insular inputs originating far beyond canonical cortical columns. Functionally, these connections bridge a long-range thalamus-to-amygdalar circuit that potentially links sensory information to valence. Our work establishes a structure-and-function foundation for investigating the insular cortex.

neuroscience↗

bioRxiv2024

Thalamic integration of basal ganglia and cerebellar circuits during motor learning

The ability to control movement and learn new motor skills is one of the fundamental functions of the brain. The basal ganglia (BG) and the cerebellum (CB) are two key brain regions involved in controlling movement, and neuronal plasticity within these two regions is crucial for acquiring new motor skills. However, how these regions interact to produce a cohesive unified motor output remains elusive. Here, we discovered that a subset of neurons in the motor thalamus receive converging synaptic inputs from both BG and CB. By performing multi-site fiber photometry in mice learning motor tasks, we found that motor thalamus neurons integrate BG and CB signals and show distinct movement-related activity. Lastly, we found a critical role of these thalamic neurons and their BG and CB inputs in motor learning and control. These results identify the thalamic convergence of BG and CB and its crucial role in integrating movement signals. HighlightsO_LIIndividual neurons in motor thalamus receive converging synaptic input from SNr and DCN projections. C_LIO_LIThalamic neurons with SNr and DCN input are concentrated at the border between VM and VAL thalamic nuclei. C_LIO_LIThalamic neurons functionally integrate SNr and DCN activity and adapt with motor learning. C_LIO_LIThalamic neurons and their inputs from SNr and DCN are critical for learning and executing motor tasks. C_LI

neuroscience↗

bioRxiv2020

High-fidelity, efficient, and reversible labeling of endogenous proteins using CRISPR-based designer exon insertion

Precise and efficient insertion of large DNA fragments into somatic cells using gene editing technologies to label or modify endogenous proteins remains challenging. Non-specific insertions/deletions (INDELs) resulting from the non-homologous end joining pathway make the process error-prone. Further, the insert is not readily removable. Here, we describe a method called CRISPR-mediated insertion of exon (CRISPIE) that can precisely and reversibly label endogenous proteins using CRISPR/Cas9-based editing. CRISPIE inserts a designer donor module, which consists of an exon encoding the protein sequence flanked by intron sequences, into an intronic location in the target gene. INDELs at the insertion junction will be spliced out, leaving mRNAs nearly error-free. We used CRISPIE to fluorescently label endogenous proteins in neurons in vivo with previously unachieved efficiency. We demonstrate that this method is broadly applicable, and that the insert can be readily removed later. CRISPIE permits protein sequence insertion with high fidelity, efficiency, and flexibility.

cell biology↗