Biology subjects

Hassan, A. R.

Publications and source records attributed to Hassan, A. R..

4 recordsLinked to original sources

bioRxiv2025

Rod photoreceptors control the ON vs OFF polarity of cone-signaling neurons

A fundamental feature of the visual system is its ability to detect image contrast. The contrast processing starts in the first synapse of the retina where parallel pathways are established to compute contrast to bright (ON pathway) and dark (OFF pathway) objects, separately transferred to morphologically identified ON and OFF cells throughout the visual system. Here, we found that response polarity in ON and OFF neurons is not fixed but rather switches dynamically to the opposite sign. The switch was not observed in rod-knockout mice, indicating that rods generate the polarity switch. We determined that neither horizontal cells nor rod-signaling pathways were responsible for the switch. Instead, we discovered that EAAT5 glutamate transporters located at photoreceptor terminals were required to produce the polarity switch. Our findings provide a new perspective on the adaptive properties of neural networks and their ability to encode contrast across the visual dynamic range.

neuroscience↗

bioRxiv2025

A characterization of mouse retinal ganglion cell types labeled with AAV tools

The mouse retina is made-up of approximately 150 types of neurons each with unique characteristics and functions in interpreting visual information. Recent efforts to categorize cell types using molecular markers, morphology, and electrophysiological response properties have provided a wealth of information and a host of tools for studying specific cell types. AAV-based approaches have several advantages over transgenic mouse lines, including ease of application to many different animal models without extensive crossing and their amenability to intersectional approaches. Here, we provide an in-depth characterization of retinal ganglion cell types labeled by two AAV vectors drawn from a recent panel of constructs with synthetic promoters. Each promoter analyzed here was derived from a gene expressed in a cell type specific manner. Using a combination of morphology, molecular markers, and electrophysiological measurement of light responses, we found that each vector labeled distinct subsets of RGCs. However, both labeled more cell types than expected from the expression pattern of the promoters endogenous gene. We then characterized the projection patterns of these RGC types to the brain, finding that each AAV type labeled distinct axonal populations. These tools provide new access to a unique subset of cells and will be instrumental to future studies analyzing their functions and connectivity.

neuroscience↗

bioRxiv2024

Melanopsin ganglion cells in the mouse retina independently evoke pupillary light reflex

PurposeThe pupillary light reflex (PLR) is crucial for protecting the retina from bright light. The intrinsic photosensitive ganglion cells (ipRGCs) in the retina mediate the PLR, which directly sense light and receive inputs from rod/cone photoreceptors. Previous work used genetic knockout mice to reveal that rod/cone photoreceptors drive transient constriction, and ipRGCs drive the sustained component. We acutely ablated photoreceptors by a chemical injection to examine the role of rod and cone photoreceptors in PLR. MethodsPLR and the multiple electrode array (MEA) recording were conducted with C57BL6/J (wildtype: WT) and Cnga3-/-; Gnat1-/- (rod/cone dysfunctional) mice. n-Nitroso-n-methylurea (MNU) was applied to C57 mice by intraperitoneal injection, and PLR was conducted after 5-7 days of injection. Three different light levels (mesopic, low photopic, and high photopic) were tested. Immunohistochemistry was conducted using the anti-Gnat1 and anti-melanopsin antibodies with DAPI. ResultsPLR was induced by all light levels we tested, and the level of constriction increased as the light level increased. After the MNU injection, PLR was not induced at mesopic light stimulus, but was fully induced by high light. The level of PLR was identical between WT and MNU mice, suggesting that ipRGCs fully contributed to the PLR at this light level. Immunohistochemistry revealed that photoreceptors were ablated by the MNU injection, but ipRGCs were preserved. The MEA recording revealed that a population of ipRGCs generated fast and robust spikes in MNU-injected retinal tissues in ex vivo. ConclusionsContrary to previous observations, our results demonstrate that ipRGCs are the major contributor to the PLR induced by high light.

neuroscience↗

bioRxiv2024

Closed-loop electrical stimulation to prevent focal epilepsy progression and long-term memory impairment

Interictal epileptiform discharges (IEDs) are ubiquitously expressed in epileptic networks and disrupt cognitive functions. It is unclear whether addressing IED-induced dysfunction could improve epilepsy outcomes as most therapeutics target seizures. We show in a model of progressive hippocampal epilepsy that IEDs produce pathological oscillatory coupling which is associated with prolonged, hypersynchronous neural spiking in synaptically connected cortex and expands the brain territory capable of generating IEDs. A similar relationship between IED-mediated oscillatory coupling and temporal organization of IEDs across brain regions was identified in human subjects with refractory focal epilepsy. Spatiotemporally targeted closed-loop electrical stimulation triggered on hippocampal IED occurrence eliminated the abnormal cortical activity patterns, preventing spread of the epileptic network and ameliorating long-term spatial memory deficits in rodents. These findings suggest that stimulation-based network interventions that normalize interictal dynamics may be an effective treatment of epilepsy and its comorbidities, with a low barrier to clinical translation. One-Sentence SummaryTargeted closed-loop electrical stimulation prevents spread of the epileptic network and ameliorates long-term spatial memory deficits.

neuroscience↗