Biology subjects

Van Hooser, S.

Publications and source records attributed to Van Hooser, S..

6 recordsLinked to original sources

bioRxiv2025

Functional architecture for speed tuning in primary visual cortex of carnivores

Perception of motion critically depends on detecting the speed and direction of moving stimuli. The primary visual cortex (V1) of some mammals, including primates and carnivores, exhibits functional organization for key receptive field properties such as orientation, direction, and spatial frequency; however, less is known about the organization of speed-tuned cells. While individual V1 neurons have been shown to exhibit speed selectivity, functional architecture for speed preference has been primarily reported in higher cortical areas such as primate area MT. Using multi-channel electrophysiology in anesthetized female ferrets, we investigated the joint tuning of V1 neurons for spatial frequency, temporal frequency, orientation/direction, and speed. We found significant clustering of cells tuned for speed and for speed preference within single electrode penetrations. We found that both simple and complex cells can exhibit speed tuning, and no strong variation across cortical layers. In reanalysis of intrinsic signal imaging data from cat V1, we observed repeating "hot spots" of high speed selectivity separated by "cold spots" with low tuning for speed. These findings indicate that a functional architecture for speed tuning is present within V1 itself and transmitted to downstream cortical regions. Significance StatementTo perceive moving objects, the visual system must detect both their direction and speed. The primary visual cortex, the first cerebral visual area to receive visual information from the retina via the lateral geniculate nucleus, plays a key role in this process. Here, we demonstrate that the primary visual cortex in carnivores contains speed-tuned neurons. Moreover, these neurons are organized into clustered "hot spots" that repeat across the cortical surface, suggesting a functional architecture for speed. While speed-tuned functional maps were previously thought to exist only in higher visual areas, such as area MT in primates, our findings reveal their presence at the level of primary visual cortex.

neuroscience↗

bioRxiv2025

Acquired Amphotericin B Resistance Attributed to a Mutated ERG3 in Candidozyma auris

First identified in 2009, Candidozyma auris (formerly Candida auris) is an emerging multidrug resistant fungus that can cause invasive infections with a crude mortality rate ranging from 30-60%. Currently, 30-50% of C. auris isolates are intrinsically resistant to amphotericin B. In this work, we characterized a clinical case of acquired amphotericin B resistance using whole genome sequencing, a large-scale phenotypic screen, comprehensive sterol profiling, and genotypic reversion using CRISPR. Data obtained in this work provides evidence that a deletion resulting in a frameshift in ERG3 contributes to the observed resistant phenotype. Characterization of this isolate also revealed a fitness cost is associated with the abrogation of ergosterol production and its replacement with other late-stage sterols. This article presents a clinical case description of amphotericin B resistance from a frameshift mutation in ERG3 in C. auris and marks an advancement in the understanding of antifungal resistance in this fungal pathogen.

genetics↗

bioRxiv2024

Latent encoding of movement in primary visual cortex

Neurons in the primary visual cortex (V1) are classically thought to encode spatial features of visual stimuli through simple population codes: each neuron exhibits a preferred orientation and preferred spatial frequency, both of which remaining invariant to other aspects of the visual stimulus. Here, we show that this simple rule does not apply to the representation of major features of stimulus motion, including stimulus direction and temporal frequency (TF). We collected an extensive dataset of cat (of either sex) V1 responses to stimuli covarying in orientation, direction, spatial frequency, and TF to assess the extent of motion selectivity. We show that preferred TF is mostly uniform across the cortical surface. Yet, in over half of V1, the preferred direction is reversed with changing stimulus TF, revealing four distinct map motifs embedded in V1s functional architecture. Similarly, despite the lack of spatial modulation for the preferred TF map and the lack of invariance for the preferred direction map, we found using convolutional neural networks that direction, TF and stimulus speed can be accurately decoded from V1 responses at all cortical locations. These findings suggest that subtle modulations of V1 activity may convey fine information about stimulus motion, pointing to a novel primary sensory encoding mechanism despite complex co-variation of responses to multiple attributes across V1 neurons. Significance StatementUnderstanding how the external world is represented in the brain has long been a central endeavor in neuroscience. In the mammalian primary visual cortex (V1), groups of neurons encode stimulus properties through changes in activity, with "preferred" stimuli eliciting maximal responses, as demonstrated for orientation and spatial frequency. Using an extensive dataset of neuronal responses, we investigated whether V1 also encodes motion speed. We found that cortical response organization remains largely invariant, with neurons exhibiting a uniform preference for temporal frequency. Yet, machine learning algorithms decode motion speed with remarkable precision, revealing that subtle, spatially distributed modulations of activity underlie speed encoding. Moreover, we show that preferred direction flips with speed across 80% of cortex, uncovering a novel co-organization of motion and direction information in V1.

neuroscience↗

bioRxiv2023

Progressive circuit hyperexcitability in mouse neocortical slice cultures with increasing duration of activity silencing

Forebrain neurons deprived of activity become hyperactive when activity is restored. Rebound activity has been linked to spontaneous seizures in vivo following prolonged activity blockade. Here we measured the time course of rebound activity and the contributing circuit mechanisms using calcium imaging, synaptic staining and whole cell patch clamp in organotypic slice cultures of mouse neocortex. Calcium imaging revealed hypersynchronous activity increasing in intensity with longer periods of deprivation. While activity partially recovered three days after slices were released from five days of deprivation, they were less able to recover after ten days of deprivation. However, even after the longer period of deprivation, activity patterns eventually returned to baseline levels. The degree of deprivation-induced rebound was age-dependent, with the greatest effects occurring when silencing began in the second week. Pharmacological blockade of NMDA receptors indicated that hypersynchronous rebound activity did not require Hebbian plasticity evoked. In single neuron recordings, input resistance roughly doubled with a concomitant increase in intrinsic excitability. Synaptic imaging of pre- and postsynaptic proteins revealed dramatic reductions in the number of presumptive synapses with a larger effect on inhibitory than seen in excitatory synapses. Putative excitatory synapses colocalizing PSD-95 and Bassoon declined by 39% and 56% following five and ten days of deprivation, but presumptive inhibitory synapses colocalizing gephyrin and VGAT declined by 55% and 73% respectively. The results suggest that with prolonged deprivation, a progressive reduction in synapse number is accompanied by a shift in the balance between excitation and inhibition and increased cellular excitability. SIGNIFICANCE STATEMENTWhen cortical activity is silenced during development, lifelong seizures often result. Here we explored whether these seizures result from overcompensation of homeostatic recovery mechanisms. Prior work showed that neurons briefly deprived of the ability to fire action potentials compensate by becoming more excitable, increasing synaptic drive and intrinsic excitability. We found that prolonged silencing of cortex produced a profound loss of synapse density, especially for inhibitory synapses, pointing to a circuit unable to maintain excitatory/inhibitory balance. These results show that homeostatic responses, which are normally restorative, can result in maladaptive circuit configurations when brought to extremes.

neuroscience↗

bioRxiv2023

Prolonged activity-deprivation causes pre- and postsynaptic compensatory plasticity at neocortical excitatory synapses

Homeostatic plasticity stabilizes firing rates of neurons, but the pressure to restore low activity rates can significantly alter synaptic and cellular properties. Most previous studies of homeostatic readjustment to complete activity silencing in rodent forebrain have examined changes after two days of deprivation, but it is known that longer periods of deprivation can produce adverse effects. To better understand the mechanisms underlying these effects and to address how presynaptic as well as postsynaptic compartments change during homeostatic plasticity, we subjected mouse cortical slice cultures to a more severe five-day deprivation paradigm. We developed and validated a computational framework to measure the number and morphology of presynaptic and postsynaptic compartments from super resolution light microscopy images of dense cortical tissue. Using these tools, combined with electrophysiological miniature excitatory postsynaptic current measurements, and synaptic imaging at the electron microscopy level, we assessed the functional and morphological results of prolonged deprivation. Excitatory synapses were strengthened both presynaptically and postsynaptically. Surprisingly, we also observed a decrement in the density of excitatory synapses, both as measured from colocalized staining of pre- and postsynaptic proteins in tissue, and from the number of dendritic spines. Overall, our results suggest that cortical networks deprived of activity progressively move towards a smaller population of stronger synapses. SIGNIFICANCE STATEMENTBlocking activity in neocortical slice cultures produced coordinated pre and postsynaptic changes at excitatory synapses. Functional and structural assays suggest that deprivation results in fewer excitatory synapses, but each is strengthened both pre- and postsynaptically. This may contribute to the emergence of epileptiform activity.

neuroscience↗

bioRxiv2021

A transcriptional constraint mechanism limits the homeostatic response to activity deprivation in mammalian neocortex

Healthy neuronal networks rely on homeostatic plasticity to maintain stable firing rates despite changing synaptic drive. These mechanisms, however, can themselves be destabilizing if activated inappropriately or excessively. For example, prolonged activity deprivation can lead to rebound hyperactivity and seizures. While many forms of homeostasis have been described, whether and how the magnitude of homeostatic plasticity is constrained remains unknown. Here we uncover negative regulation of cortical network homeostasis by the PARbZIP family of transcription factors. In cortical slice cultures made from knockout mice lacking all three of these factors, the network response to prolonged activity withdrawal measured with calcium imaging is much stronger, while baseline activity is unchanged. Whole cell recordings reveal an exaggerated increase in the frequency of miniature excitatory synaptic currents reflecting enhanced upregulation of recurrent excitatory synaptic transmission. Genetic analyses reveal that two of the factors, Hlf and Tef, are critical for constraining plasticity and for preventing life-threatening seizures. These data indicate that transcriptional activation is not only required for many forms of homeostatic plasticity but is also involved in restraint of the response to activity deprivation.

neuroscience↗