Neurobiochemistry of memory and learning through synaptic plasticity

Abstract

The biochemical basis of memory formation has fascinated neuroscientists since Santiago Ramón y Cajal first proposed that learning modifies synaptic connections over a century ago. This research investigated molecular mechanisms underlying long-term potentiation (LTP) and long-term depression (LTD) in hippocampal slice preparations, focusing on the modulatory role of brain-derived neurotrophic factor (BDNF). Hippocampal slices from adult Wistar rats were subjected to high-frequency stimulation (LTP induction) or low-frequency stimulation (LTD induction) with or without BDNF supplementation (50 ng/mL). Synaptic responses were recorded for 240 minutes post-stimulation, and tissue was harvested for biochemical analysis of signaling pathway activation. BDNF significantly enhanced LTP magnitude by 48.3% (262% vs 182% of baseline at 60 minutes) and prolonged LTD expression by 34.7%. Phosphorylation of CaMKII, ERK1/2, and CREB showed BDNF-dependent enhancement, with CaMKII activation increased by 67.2% compared to control stimulation. These findings elucidate how BDNF orchestrates multiple signaling cascades to strengthen the biochemical foundation of memory consolidation.