Abstract
Abstract
Cholinergic degeneration contributes to hippocampal circuit dysfunction in Alzheimer’s disease (AD). Ganglioside GM1 modulates membrane signaling and synaptic function, yet its acute effects on hippocampal neuronal activity under cholinergic-deficient conditions remain unclear. Using in vivo single-unit recordings in urethane-anesthetized male rats, extracellular single-unit activity was recorded from CA1 pyramidal neurons before and after systemic GM1 administration. We examined whether systemic GM1 alters spontaneous firing of CA1 pyramidal neurons in a nucleus basalis magnocellularis (NBM) lesion model of cholinergic hypofunction. GM1 (2, 5, 10 mg/kg, i.p.) produced dose-dependent increases in firing rate. Linear mixed-effects modeling, accounting for multiple neurons per animal, revealed a significant main effect of Time (F
1,79
= 41.33,
p
2
= 0.34) and a significant Dose × Time interaction (F
3,79
= 3.28,
p
= 0.025, partial η
2
= 0.11). Notably, NBM-lesioned animals exhibited amplified responses, particularly at 2 mg/kg (Δ = 7.22 ± 1.82 Hz), whereas control animals showed minimal change at this dose. GM1-induced increases remained within reported physiological firing ranges under urethane anesthesia. These findings demonstrate that GM1 enhances hippocampal CA1 excitability in a dose- and state-dependent manner, with heightened responsiveness in cholinergic-compromised networks. The results support the concept that membrane-targeting interventions may modulate dysfunctional circuits depending on baseline network state.