Alterations in Synaptic AMPA Receptor Function Following Prenatal Cannabinoid Exposure: Implications for Neurodevelopmental Deficits
Disciplines
Cognitive Psychology | Psychology
Abstract (300 words maximum)
The increasing legalization of cannabis has led to a marked rise in prenatal cannabinoid exposure (PCE), a trend projected to continue. PCE has been associated with long-term neurodevelopmental impairments, particularly affecting learning and memory; however, no therapeutic strategies currently exist to mitigate these cognitive deficits. This study examines the impact of PCE on the biophysical properties of synaptic AMPA (α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid) receptors, which are critical mediators of excitatory neurotransmission, synaptic plasticity, and memory processes. To elucidate the mechanisms underlying AMPA receptor dysfunction, pregnant Sprague Dawley rats were administered either sesame oil (control) or 5 mg/kg Δ9-tetrahydrocannabinol (THC) via oral gavage from gestational day 5 to postnatal day 9. Electrophysiological recordings were performed on hippocampal synaptosomal AMPA receptors in adolescent offspring (postnatal days 40–50) from both experimental groups. Results demonstrated a significant reduction in AMPA receptor open channel probability and conductance in PCE offspring relative to controls. These findings indicate that prenatal THC exposure disrupts AMPA receptor function, potentially impairing synaptic plasticity mechanisms such as long-term potentiation (LTP) that is required for memory formation. Given the pivotal role of AMPA receptors in memory encoding, PCE-induced alterations in receptor function may contribute to the cognitive deficits observed in exposed offspring. This study provides critical insights into the synaptic pathophysiology underlying PCE-related learning and memory impairments, highlighting the urgent need for targeted interventions to counteract the neurodevelopmental consequences of prenatal cannabinoid exposure.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Vishnu Suppiramaniam
Alterations in Synaptic AMPA Receptor Function Following Prenatal Cannabinoid Exposure: Implications for Neurodevelopmental Deficits
The increasing legalization of cannabis has led to a marked rise in prenatal cannabinoid exposure (PCE), a trend projected to continue. PCE has been associated with long-term neurodevelopmental impairments, particularly affecting learning and memory; however, no therapeutic strategies currently exist to mitigate these cognitive deficits. This study examines the impact of PCE on the biophysical properties of synaptic AMPA (α-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid) receptors, which are critical mediators of excitatory neurotransmission, synaptic plasticity, and memory processes. To elucidate the mechanisms underlying AMPA receptor dysfunction, pregnant Sprague Dawley rats were administered either sesame oil (control) or 5 mg/kg Δ9-tetrahydrocannabinol (THC) via oral gavage from gestational day 5 to postnatal day 9. Electrophysiological recordings were performed on hippocampal synaptosomal AMPA receptors in adolescent offspring (postnatal days 40–50) from both experimental groups. Results demonstrated a significant reduction in AMPA receptor open channel probability and conductance in PCE offspring relative to controls. These findings indicate that prenatal THC exposure disrupts AMPA receptor function, potentially impairing synaptic plasticity mechanisms such as long-term potentiation (LTP) that is required for memory formation. Given the pivotal role of AMPA receptors in memory encoding, PCE-induced alterations in receptor function may contribute to the cognitive deficits observed in exposed offspring. This study provides critical insights into the synaptic pathophysiology underlying PCE-related learning and memory impairments, highlighting the urgent need for targeted interventions to counteract the neurodevelopmental consequences of prenatal cannabinoid exposure.