Biology subjects

Deemyad, T.

Publications and source records attributed to Deemyad, T..

4 recordsLinked to original sources

bioRxiv2026

Autism associated Cntnap2 deletion disrupts vestibular sensory signaling and spatial cognition in mice

Autism spectrum disorder (ASD) is frequently accompanied by sensory and motor abnormalities, including impaired balance, postural control, and spatial orientation, that are often attributed largely to altered central circuitry. Emerging evidence, however, suggests that peripheral sensory dysfunction can also shape ASD related behavioral phenotypes. Here, we tested whether loss of the ASD associated gene Cntnap2/Caspr2 alters vestibular signaling in Cntnap2-/- mice. Developmental transcriptomic analysis showed that Cntnap2 is expressed in vestibular sensory organs and increases during the first postnatal month, coincident with vestibular pathway maturation. Vestibular sensory evoked potentials revealed reduced response amplitudes and prolonged latencies in Cntnap2-/- mice, indicating impaired peripheral afferent responses to transient linear acceleration. Cntnap2-/- mice also showed delayed contact righting, reduced ocular counter roll, and increased hindlimb slips and compensatory tail excursions during balance beam walking, whereas rotational vestibulo-ocular reflex gain and phase were preserved. These vestibular and balance abnormalities were accompanied by reduced novel arm preference in the Y maze and severe impairment of Barnes maze acquisition, consistent with impaired spatial learning. Together, these findings identify Cntnap2/Caspr2 as a regulator of vestibular sensory signaling and support a model in which disrupted peripheral vestibular input, likely acting together with central effects of Cntnap2 loss, contributes to sensorimotor and spatial cognitive phenotypes relevant to ASD.

neuroscience↗

bioRxiv2024

Striatal output regulates the postnatal maturation of cortical circuits

The dorsomedial prefrontal cortex (dmPFC) is interconnected with the basal ganglia (BG) through large-scale circuit loops that regulate critical motor and cognitive functions. In mice, these circuits undergo extensive postnatal maturation with marked changes in neural activity and expansion of synaptic connectivity. While cortical activity is known to regulate the development of downstream striatal circuits, the role of the basal ganglia in cortical maturation remains unknown. Here, we used mesoscale two-photon microscopy and whole-cell electrophysiology to examine whether striatal output during early postnatal development impacts the activity and maturation of upstream dmPFC circuits. We found that ablating spiny projection neurons of the direct or indirect pathways of the striatum during the first two postnatal weeks causes bidirectional changes in dmPFC neural activity, similar to observations in mature circuits. In addition, these manipulations alter the maturation of synaptic connectivity of dmPFC layer 2/3 pyramidal neurons, shifting the balance of excitation and inhibition of cortical circuits. These findings demonstrate that striatal output modulates the activity of cortical circuits during early postnatal development and suggest a regulatory role of the basal ganglia in the establishment of cortical circuits.

neuroscience↗

bioRxiv2020

Lateralized decrease of parvalbumin+ cells in the somatosensory cortex of ASD models is correlatedwith unilateral tactile hypersensitivity

Inhibitory control of excitatory networks contributes to cortical functions. Increasing evidence indicates that parvalbumin expressing (PV+) basket cells (BC) are a major player in maintaining the balance between excitation (E) and inhibition (I) in the cortex. Disruption of E/I balance in cortical networks is believed to be a hallmark of autism spectrum disorders (ASD) and may contribute to sensory alterations seen in ASD. Here, we report a lateralized decrease in the number of PV+ BCs in L2/3 of the somatosensory cortex in the dominant hemisphere of adult Shank3-/- and Cntnap2-/- mouse models of ASD. The dominant hemisphere was identified during a reaching task to establish each animals dominant forepaw. Double labeling with anti-PV antibody and a biotinylated lectin (i.e., VVA) showed that the number of BCs was not different but rather, some BCs did not express detectable levels of PV (PV-), resulting in an elevated number of PV- VVA+ basket cells. This lateralized reduction was not observed in the number of interneurons from the other two major groups that express somatostatin or the serotonergic receptor 5HT3a. Finally, we showed that dominant hind paws had higher mechanical sensitivity (i.e., lower mechanical thresholds measured with von Frey test) but no difference in thermal sensitivity (measured with Hargreaves test) when compared to the other hind paw. This mechanical hypersensitivity in the dominant paw correlated with the decrease in the number of PV+ interneurons and reduced PV expression in the corresponding cortex. Together, these results suggest that the sensory hypersensitivity in ASD could be due to decreased inhibitory inputs to the dominant somatosensory cortex.

neuroscience↗

bioRxiv2018

Astrocytes integrate and drive neural activity

Many brain functions depend on the ability of neural networks to temporally integrate transient inputs to produce sustained discharges. This can occur through cell-autonomous mechanisms in individual neurons or through reverberating activity in recurrently connected neural networks. We report a third mechanism involving temporal integration of neural activity by a network of astrocytes. Previously, we showed that some types of interneurons can generate long-lasting trains of action potentials for tens of seconds (\"barrage firing\") following repeated depolarizing stimuli. Here, we show that calcium signaling in an astrocytic network correlates with barrage firing; that active depolarization of astrocyte networks by chemical or optogenetic stimulation enhances barrage firing; and that chelating internal calcium, inhibiting release from internal stores, or inhibiting GABA transporters or metabotropic glutamate receptors inhibited barrage firing. Thus, through complex molecular processes, networks of interconnected astrocytes influence the spatiotemporal dynamics of neural networks by directly integrating neural activity and driving long-lasting barrages of action potentials in some populations of inhibitory interneurons.

neuroscience↗