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<p>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&#xa0;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<sub>1,79</sub> = 41.33, <i>p</i> &lt; 0.001, partial η<sup>2</sup> = 0.34) and a significant Dose × Time interaction (F<sub>3,79</sub> = 3.28, <i>p</i> = 0.025, partial η<sup>2</sup> = 0.11). Notably, NBM-lesioned animals exhibited amplified responses, particularly at 2 mg/kg (Δ = 7.22 ± 1.82&#xa0;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.</p>

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Dose- and state-dependent enhancement of hippocampal CA1 pyramidal neuron excitability by GM1 ganglioside in male rats with cholinergic lesions

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Sedigheh Ashkavandi,
  • Ahmad Ali Moazedi,
  • Saeed Semnanian,
  • Saeedeh Abdolahpour,
  • Maryam Gholami

摘要

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 (F1,79 = 41.33, p < 0.001, partial η2 = 0.34) and a significant Dose × Time interaction (F3,79 = 3.28, p = 0.025, partial η2 = 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.