Biology subjects

Houser, G.

Publications and source records attributed to Houser, G..

4 recordsLinked to original sources

bioRxiv2026

Cue-guided performance is disrupted during pedunculotegmental-induced motor arrest

Optogenetic stimulation of the rostral pedunculotegmental nucleus (PTg) induces global motor arrest, but it remains unclear whether this is merely a suppression of motor activity or a broader disruption of brain processes required to guide action. We developed a visuospatial cue task for rats, to test if sensory information presented during PTg-induced arrest can guide later responses. Here, we show that optogenetic stimulation during cue presentation reduces accuracy to chance level. By moving stimulation to only before or only after the cue, we found that performance was only affected when stimulation and cue presentation overlapped, that rats recover cue-guided behavior almost immediately at the end of stimulation, and that stimulation does not appear to abolish responses based on cue information acquired before arrest. These findings indicate that stimulation of the rostral PTg does not only pause motor output but transiently disrupts the ability to process and use cue information effectively.

neuroscience↗

bioRxiv2024

Spatial and network principles behind neural generation of locomotion

Generation of locomotion is a fundamental function of the spinal cord, yet the underlying principles remain unclear. In particular, the relationship between neuronal cell types, networks and functions has been difficult to establish1,2. Here, we propose principles by which functions arise primarily from spatial features of the cord. First, we suggest that projections of distinct cell types constitute an asymmetrical "Mexican hat" topology, i.e. local excitation and surrounding inhibition with dissimilar length of projection along the rostro-caudal axis. Second, this projection topology constitutes the mechanism of rhythm- and pattern generation of mammalian locomotion. Third, the role of segregation of cell types in the transversal plane is for descending fibers to find appropriate targets. Modulation of these targets allows control of motor activity by adjusting the symmetry of the projection topology. We extract these principles via a model of the mouse spinal cord, where networks are constructed by probabilistic sampling of synaptic connections from cell-specific projection patterns, which are based on previous studies3, 4. The cell-type distributions are derived from single-cell RNA sequencing combined with spatial transcriptomics5. We find that essential aspects of locomotion are readily reproduced and controlled without requiring parameter optimization, and several experimental observations can now be explained mechanistically. Further, two main features are predicted: propagating bumps of neural activity during rhythmical activity and formation of static bumps during arrest and posture. Besides linking cell types, structure and function, we propose our approach as a new theoretical framework for motor control.

neuroscience↗

bioRxiv2022

Characteristics and Impact of the rNST GABA Network on Neural and Behavioral Taste Responses

The rostral nucleus of the solitary tract (rNST), the initial CNS site for processing gustatory information, is comprised of two major cell types, glutamatergic excitatory and GABAergic inhibitory neurons. Many investigators have described taste responses of rNST neurons, but the phenotypes of these cells were unknown. The current investigation used mice expressing ChR2 under the control of GAD65, a synthetic enzyme for GABA. In vivo single-unit recording of rNST cells during optogenetic stimulation allowed us to address two important questions: (1) what are the gustatory response characteristics of "optotagged", putative GABAergic (G+TASTE) neurons? and (2) how does optogenetic activation of the rNST GABA network impact taste responses in non-GABAergic (G-TASTE) neurons? We observed that chemosensitive profiles of G+TASTE neurons were similar to non-GABA taste neurons but had much lower response rates. We further observed that there was a population of GABA cells unresponsive to taste stimulation (G+UNR) and located more ventrally in the nucleus. Activating rNST inhibitory circuitry suppressed gustatory responses of G-TASTE neurons across all qualities and types of chemosensitive neurons. Tuning curves were modestly sharpened but the overall shape of response profiles and the ensemble pattern remained highly stable. These neurophysiological effects were consistent with the behavioral consequences of activating GAD65-expressing inhibitory neurons using DREADDs. In a brief-access licking task, concentration-response curves to both palatable (sucrose, maltrin) and unpalatable (quinine) stimuli were shifted to the right when GABA neurons were activated. Thus, the rNST GABAergic network is poised to modulate taste intensity across the qualitative and hedonic spectrum. SIGNIFICANCE STATEMENTThe rNST, the CNS gateway for taste, is rich in GABAergic neurons and synapses. Our in vivo recordings from GAD65/ChR2 mice reveal that gustatory response profiles of optotagged GABAergic neurons resemble non-GABAergic neurons, but with much reduced amplitudes. A novel population of GABA neurons were unresponsive to oral stimulation suggesting they are targets for centrifugal influences. Activating rNST inhibitory circuitry modestly sharpened gustatory tuning but preserved the ensemble pattern for taste quality despite markedly suppressed responses. In behaving mice, activating rNST GAD65-expressing neurons with DREADDs shifted response-concentration curves for palatable and unpalatable stimuli, but preserved appropriate behaviors. These observations unveil previously unknown features of rNST GABA cells and demonstrate substantial inhibitory modulation at the first central taste relay.

neuroscience↗

bioRxiv2019

Single-cell resolution view of the transcriptional landscape of developing Drosophila eye.

Faithful and reliable quantification of gene expression at a single-cell level is an outstanding challenge in developmental biology. Most existing approaches face a trade-off between the signal to noise ratio, resolution, and sensitivity. Here, we present a novel approach for in situ quantification of gene expression in a developing tissue. Our pipeline combines computational prediction of transcription factor targets, gene tagging, fluorescent reporter imaging, state-of-the-art image analysis, and automated cell-type identification. By applying this approach to identify the sequence of quantitative changes in gene expression which govern the development of the Drosophila neural retina, we demonstrate the feasibility of our method. We analyze the targets of Atonal (Ato), a transcription factor that controls the transition from eye disc progenitor cell to photoreceptor neurons. We utilized recombineering and genomic engineering to tag all predicted Ato targets with novel transcriptional reporters. These reporters enable following the expression of both regulator and regulated genes to accurately quantify their expression levels in individual cells. Our complete computational pipeline identifies nuclei in the eye discs and detects different states of cells as they progress through differentiation. Based on detailed gene expression analysis, our technique revealed genes likely to be direct Ato targets and provided insight into how gene expression changes drive the specification of photoreceptors.

developmental biology↗