Cholinergic Control in Developing Prefrontal–Hippocampal Networks

Abstract

The cholinergic drive enhances input processing in attentional and mnemonic context by interacting with the activity of prefrontalhippocampal networks. During development, acetylcholine modulates neuronal proliferation, differentiation, and synaptic plasticity, yet its contribution to the maturation of cognitive processing resulting from early entrainment of neuronal networks in oscillatory rhythms remains widely unknown. Here we show that cholinergic projections growing into the rat prefrontal cortex (PFC) toward the end of the first postnatal week boost the generation of nested gamma oscillations superimposed on discontinuous spindle bursts by acting on functional muscarinic but not nicotinic receptors. Although electrical stimulation of cholinergic nuclei increased the occurrence of nested gamma spindle bursts by 41%, diminishment of the cholinergic input by either blockade of the receptors or chronic immunotoxic lesion had the opposite effect. This activation of locally generated gamma episodes by direct cholinergic projections to the PFC was accompanied by indirect modulation of underlying spindle bursts via cholinergic control of hippocampal theta activity. With ongoing maturation and switch of network activity from discontinuous bursts to continuous theta-gamma rhythms, accumulating cholinergic projections acting on both muscarinic and nicotinic receptors mediated the transition from high-amplitude slow to low-amplitude fast rhythms in the PFC. By exerting multiple actions on the oscillatory entrainment of developing prefrontal-hippocampal networks, the cholinergic input may refine them for later gating processing in executive and mnemonic tasks.

Developmental dysfunction of prefrontal–hippocampal networks in mouse models of mental illness

“…These findings indicate that the network activity in hippocampal CA1 area is compromised in neonatal one‐hit Df16 as well as dual‐hit mice. The absence of firing deficits in these mice confirms the minor contribution of CA1 neurons to the generation of discontinuous network oscillations (Janiesch, Kruger, Poschel, & Hanganu‐Opatz, ).…”

Hypoxia-Ischemia Disrupts Directed Interactions within Neonatal Prefrontal-Hippocampal Networks

“…HI reduced the prefrontal neuronal firing and gamma-band oscillatory entrainment of local networks. Moreover, HI decreased the coupling synchrony within developing prefrontal-hippocampal networks and impaired the theta drive from the HP to the PFC, which previously has been shown to facilitate the functional maturation of the PFC [23], [24], [36]. Thus, disruption of functional communication within prefrontal-hippocampal networks during a “critical” developmental period of directed interactions might act as underlying mechanism of later HI-induced cognitive disability.…”

Cortical Development, Electroencephalogram Rhythms, and the Sleep/Wake Cycle

“…Many noradrenergic neurons in the rat locus coeruleus are not spontaneously active during the first postnatal week, and adult-like rates of tonic firing are only reached at ~P20 (43). Similarly, cholinergic fibers grow significantly in the supragranular layers only during the second postnatal week (44), and a mature cholinergic innervation is reached only between the third and fourth week (45). These findings suggest that it is only when subcortical areas “take full control” of the maturing cortex that behavior (sleep/wake) and cortical activity no longer dissociate.…”