Wednesday, April 2, 2025
4/2/2025
Enhancing the function of hippocampal neurons after TBI - Abstract. The cognitive impairments that occur after a concussion (or mild TBI) can be long-lasting, and can interfere with every day activities. These deficits, especially memory dysfunction, are often due to perturbations of hippocampal function. In vivo recordings of neural activity in behaving animals have demonstrated that the firing of a subset of pyramidal neurons in the hippocampus increases when an animal moves through its environment. These cells, referred to as “place cells”, display localized firing patterns (i.e. place fields) that the animal uses to recognize an environment. Thus, a failure to form stable place fields has been linked to learning and memory dysfunction. Evidence has shown that theta oscillations (a rhythmic firing pattern seen in the hippocampus) play an important role in modulating place field stability, and in learning and memory. This rhythm is established by connections between inhibitory neurons present in the medial septum and the hippocampus. We present supportive results to indicate that the number of parvalbumin-expressing inhibitory neurons in the CA1 subfield of the hippocampus is decreased after a fluid percussion injury (FPI), an effect that occurs in the absence of overt loss of pyramidal neurons. Associated with this loss, electrophysiological recordings revealed a decrease in theta power and place cell instability that are evident for weeks after brain injury. The transcription factor cAMP response element binding protein (CREB) is phosphorylated and increases neuroplasticity-related gene expression following phosphorylation by specific protein kinases, and has been shown to be critical for place cell stability. Based on these results, we propose to test the hypothesis that stimulation of hippocampal CA1 pyramidal neurons at theta frequency or pharmacological potentiation of CREB will increase place cell function and improve memory formation in the chronic stage of FPI. The results from these proposed studies will reveal the neural basis for memory dysfunction and potential pharmacological strategy to restore neural function and improve learning and memory during subacute/chronic stage of traumatic brain injury.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).