Jun, D. | Search bioRxiv

bioRxiv2024

Enhancement of spatial learning by 40 Hz visual stimulation requires parvalbumin interneuron-dependent hippocampal neurogenesis

Acute and short-term rhythmic 40 Hz light flicker stimulation has shown promising results in alleviating cognitive impairments in mouse models of Alzheimers disease (AD), stroke, and autism spectrum disorders (ASD). Understanding the long-term impacts and underlying mechanisms is crucial to progress this approach for potential human therapeutic applications. Here, we show that prolonged exposure to 40 Hz light flicker (1 hour per day for 30 days) significantly improved spatial learning and neurogenesis in the dentate gyrus (DG) without harmful behavioral side effects. Mice with transgenic deletion of doublecortin-positive cells (DCXDTR) in the adult hippocampus failed to exhibit enhanced neurogenesis and spatial learning with 40 Hz stimulation. Inactivation or knockout of GABAergic parvalbumin (PV) interneurons reduced the effects of 40 Hz entrainment and neurogenesis enhancement. Mechanistically, the stimulation did not alter the regional microvessel blood flow but significantly raised PV excitability and GABA levels and enhanced inhibitory transmission in the DG. Blocking GABAA receptors reversed the improvements in spatial learning and neurogenesis. These data showed that long-term exposure to 40 Hz light flicker enhances spatial learning through PV-dependent adult neurogenesis, which requires elevated GABA as a critical neurochemical mechanism for sustaining adult neurogenesis. In briefRhythmic 40 Hz light flicker alleviates cognitive impairments in diverse animal models of neurological diseases. Understanding its long-term effects and mechanisms is vital for advancing its therapeutic potential for humans. Here, we show that prolonged exposure to this flicker improves spatial learning and boosts adult neurogenesis in the dentate gyrus. Activation of PV interneurons and GABAergic support for the newborn immature neurons underlie this effect, demonstrating lasting benefits for the treatment of neurological diseases. HighlightsO_LILong-term exposure to 40 Hz light flicker significantly improved spatial learning and neurogenesis in the hippocampus, devoid of adverse effects. C_LIO_LIThe 40 Hz light flicker evoked adult neurogenesis requires the activity of GABAergic inhibitory PV interneurons. C_LIO_LIThe 40 Hz light flicker raised GABA levels and enhanced inhibitory transmission in the DG. C_LIO_LIIncreased GABA serves as a vital neurochemical mechanism to support adult neurogenesis. C_LI

neuroscience↗

bioRxiv2022

Patterns of Arc mRNA expression in the rat brain following dual recall of fear- and reward-based socially acquired information

The ability to learn new information and behaviors is a vital component of survival in most animal species. This learning can occur via direct experience or through observation of another individual (i.e., social learning). While research focused on understanding the neural mechanisms of direct learning is prevalent, less work has aimed at understanding the brain circuitry mediating the acquisition and recall of socially acquired information. We aimed to further elucidate the mechanisms underlying recall of socially acquired information by having rats sequentially recall a socially transmitted food preference (STFP) and a fear association via fear conditioning by-proxy (FCbP). Brain tissue was processed for mRNA expression of the immediate early gene (IEG) Arc, which reliably expresses in the cell nucleus following transcription before migrating to the cytoplasm over the next 25 minutes. Given this timeframe, we were able to identify whether Arc transcription was triggered by STFP recall, FCbP recall, or following recall of both memories. Surprisingly - and contrary to past research examining expression of other IEGs following STFP or FCbP recall separately - we found no differences in any of the Arc expression measures across a number of prefrontal regions and the vCA3 of the hippocampus between controls, demonstrators, and observers, though we did detect an overall effect of sex in a number of regions. We theorize that these results may indicate that relatively little Arc-dependent neural restructuring is taking place in the prefrontal cortices following recall of a recently socially acquired information or directly acquired fear associations in these areas.

neuroscience↗