Biology subjects

Hernan, A.

Publications and source records attributed to Hernan, A..

3 recordsLinked to original sources

bioRxiv2025

Normalization of Prefrontal Network Dynamics Prevents Cognitive Impairments After Developmental Insult

The neurodevelopmental period is highly sensitive; insults during this period impair neural network connectivity, causing lasting cognitive deficits associated with many neuropsychiatric disorders. Medial prefrontal cortex (mPFC) networks subserve flexible behavior, but the mechanisms underlying their disruption after developmental insults remain unclear. We used an early-life seizure (ELS) model to investigate how mPFC networks become impaired and tested whether adrenocorticotropic hormone (ACTH), a clinically relevant neuroprotective peptide, could restore network function. Using in-vivo single-unit recordings during baseline and fear extinction learning, we found ELS-induced dysfunction was characterized by reduced neuronal firing, rigid spike-timing, and weakened functional connectivity, all predicting impaired extinction learning. ACTH treatment prevented these deficits, preserving dynamic spike-timing, flexible connectivity, and network organization. Advanced graph neural network modeling identified neuronal features predictive of cognitive outcomes, revealing potential biomarkers broadly relevant to other developmental disorders. These findings highlight fundamental mechanisms of mPFC network dysfunction and emphasize the translational potential of targeting network dynamics to restore cognition in neurodevelopmental disorders.

neuroscience↗

bioRxiv2024

Disrupted Hippocampal-Prefrontal Networks In A Rat Model Of Fragile X Syndrome: A Study Linking Neural Dynamics To Autism-Like Behavioral Impairments

Fragile X Syndrome (FXS) is associated with autism spectrum disorder (ASD) symptoms that are associated with cognitive, learning, and behavioral challenges. We investigated how known molecular disruptions in the Fmr1 knockout (FMR-KO) rat model of FXS negatively impact hippocampal-prefrontal cortex (H-PFC) neural network activity and consequent behavior. MethodsFMR-KO and control rats underwent a battery of behavioral tests assessing sociability, memory, and anxiety. Single-unit electrophysiology recordings were then conducted to measure patterns of neural activity in H-PFC circuit. Advanced mathematical models were used to characterize the patterns that were then compared between groups using generalized linear mixed models. ResultsFMR-KO rats demonstrated significant behavioral deficits in sociability, spatial learning, and anxiety, aligning with symptoms of ASD. At the neural level, these rats exhibited abnormal firing patterns in the H-PFC circuit that is critical for learning, memory, and social behavior. The neural networks in FMR-KO rats were also less densely connected and more fragmented, particularly in hippocampal-PFC correlated firing. These findings suggest that disruptions in neural network dynamics underlie the observed behavioral impairments in FMR-KO rats. ConclusionFMR-KO significantly disrupts several characteristics of action potential firing in the H-PFC network, leading to deficits in social behavior, memory, and anxiety, as seen in FXS. This disruption is characterized by less organized and less resilient hippocampal-PFC networks. These findings suggest that therapeutic strategies aimed at normalizing neural dynamics, such as with brain stimulation, could potentially improve behavior and cognitive functions in autistic individuals. HIGHLIGHTSO_LIFragile X Syndrome is associated with autism, cognitive challenges and anxiety C_LIO_LIThe loss of Fmr1 protein disrupts processes involved in building neural networks C_LIO_LIThe consequence is abnormal neural dynamics in hippocampal-prefrontal cortex networks C_LIO_LINormalization of dynamics could improve outcomes in FXS and ASD C_LI

neuroscience↗

bioRxiv2019

Distributed dynamic coding for spatial working memory in hippocampal-prefrontal networks

Spatial working memory (SWM) is a central cognitive process during which the hippocampus and prefrontal cortex (PFC) encode and maintain spatial information for subsequent decision-making. This occurs in the context of ongoing computations relating to spatial position, recall of long-term memory, attention, amongst many others. To establish how intermittently presented information is integrated with ongoing computations we recorded single units, in both hippocampus and PFC, in control rats and those with a brain malformation during performance of a SWM task. Neurons that encode intermittent task parameters are also well-modulated in time and incorporated into a functional network across regions. Our results implicate a model in which ongoing oscillatory coordination among neurons in the hippocampal-PFC network defines a functional network that is poised to receive sensory inputs that are then integrated and multiplexed as working memory. These dynamics are systematically altered in disease and may provide potential targets for stimulation-based therapies.

neuroscience↗