Biology subjects

Cook, E. P.

Publications and source records attributed to Cook, E. P..

4 recordsLinked to original sources

bioRxiv2025

Visual field specializations in mouse dLGN

Neural circuits throughout the visual system process features differently depending on where they appear in the visual field. While such location-specific processing exists in retina and in superior colliculus, the dorsal lateral geniculate nucleus (dLGN) is thought to lack this specialization. Here, we show systematic visual field biases in dLGNs representation of spatial frequency, orientation, direction, and temporal frequency. Using axon-localized calcium indicators and widefield imaging, we discovered that dLGN boutons show systematic gradients in feature selectivity across the visual cortex (V1), while its retinal inputs lack such gradients for these features. Selective disruption of V1 feedback to dLGN perturbed gradient structure and magnitude. These results suggest that dLGN circuits transform uniformly distributed retinal feature inputs into spatially-biased representations along with cortical feedback. dLGN feature biases would allow a functional stream to detect ethologically salient visual inputs.

neuroscience↗

bioRxiv2024

Serotonergic neurons in the dorsal raphe regulate visual attention

Visual attention enhances the neural representation of salient stimuli within the visual cortex. It is generally thought that this enhancement is driven by glutamatergic feedback from frontal cortical areas. Here we report the unexpected observation that dorsal raphe (DR) derived serotonin (5HT) controls visual attention. We developed a behavioral model that captured the way mice allocated attention to cued and uncued visual locations and features. Simultaneous photometry showed reduced DR activity when mice deployed attention to the cued locations and features, whereas high DR activity was observed when mice were less attentive. Optogenetic excitation of DR-5HT neurons impaired attention to the cue and degraded behavioral performance, while optogenetic suppression improved attention and performance. A genetically encoded sensor of 5HT release showed reduced 5HT levels in visual cortex when mice attend and detect stimuli. These results demonstrate that DR-5HT neurons are members of the brains attentional circuit and suggest that 5HT is a novel biological carrier of visual attention.

neuroscience↗

bioRxiv2024

Cadherin 4 assembles a family of color-selective retinal circuits that respond to light offset.

Retinal interneurons and projection neurons (retinal ganglion cells, RGCs) connect in specific combinations in a specialized neuropil called the inner plexiform layer (IPL). The IPL is divided into multiple sublaminae, with neurites of each neuronal type confined to one or a few layers. This laminar specificity is a major determinant of circuit specificity and circuit function. Using a combination of approaches we show that RGCs targeting IPL sublamina 1 and 3a express the adhesion molecule cadherin 4 (Cdh4). Using calcium imaging and iterative immunostaining, we classified Cdh4-RGCs into 9 types that each encode unique aspects of dark visual stimuli. Cdh4 loss selectively disrupted the layer- targeting of these RGCs, reduced their synaptic inputs from interneurons, and severely altered their visual responses. Overexpression of Cdh4 in other retinal neurons directed their neurites to s1-3a through homophilic interactions. Taken together, these results demonstrate that Cdh4 is a novel layer targeting system for nearly a third of all RGC.

neuroscience↗

bioRxiv2022

Impaired dendritic spike generation in the Fragile X prefrontal cortex is due to loss of dendritic sodium channels

Patients with Fragile X syndrome, the leading monogenetic cause of autism, suffer from impairments related to the prefrontal cortex including working memory and attention. Synaptic inputs to the distal dendrites of layer 5 pyramidal neurons in the prefrontal cortex have a weak influence on the somatic membrane potential. To overcome this filtering, distal inputs are transformed into local dendritic Na+ spikes, which propagate to the soma and trigger action potential output. Layer 5 extratelencephalic (ET) PFC neurons project to the brainstem and various thalamic nuclei and are therefore well positioned to integrate task-relevant sensory signals and guide motor actions. We used current clamp and outside-out patch clamp recording to investigate dendritic spike generation in ET neurons from male wild type and Fmr1 knockout (FX) mice. The threshold for dendritic spikes was more depolarized in FX neurons compared to wild type. Analysis of voltage responses to simulated in vivo "noisy" current injections showed that a larger dendritic input stimulus was required to elicit dendritic spikes in FX ET dendrites compared wild type. Patch clamp recordings revealed that the dendritic Na+ conductance was significantly smaller in FX ET dendrites. Taken together, our results suggest that input-output transformation is impaired in ET neurons of the PFC in FX mice. Considering our prior findings that somatic D-type K+ and dendritic HCN-channel function is reduced in ET neurons, we suggest that the integration of information by PFC circuits is fundamentally altered in Fragile X syndrome. KEY POINTSO_LIDendritic spike threshold is depolarized in Layer 5 PFC neurons in FX mice C_LIO_LISimultaneous somatic and dendritic recording with white noise current injections revealed that larger dendritic stimuli were required to elicit dendritic spikes in FX ET neurons C_LIO_LIOutside-out patch clamp recording revealed that dendritic sodium conductance density was lower in FX ET neurons C_LI

neuroscience↗