Medial septum regulates the hippocampal spatial representation

Abstract

The hippocampal circuitry undergoes attentional modulation by the cholinergic medial septum. However, it is unclear how septal activation regulates the spatial properties of hippocampal neurons. We investigated here what is the functional effect of selective-cholinergic and non-selective septal stimulation on septo-hippocampal system. We show for the first time selective activation of cholinergic cells and their differential network effect in medial septum of freely-behaving transgenic rats. Our data show that depolarization of cholinergic septal neurons evokes frequency-dependent response from the non-cholinergic septal neurons and hippocampal interneurons. Our findings provide vital evidence that cholinergic effect on septo-hippocampal axis is behavior-dependent. During the active behavioral state the activation of septal cholinergic projections is insufficient to evoke significant change in the spiking of the hippocampal neurons. The efficiency of septo-hippocampal processing during active exploration relates to the firing patterns of the non-cholinergic theta-bursting cells. Non-selective septal theta-burst stimulation resets the spiking of hippocampal theta cells, increases theta synchronization, entrains the spiking of hippocampal place cells, and tunes the spatial properties in a timing-dependent manner. The spatial properties are augmented only when the stimulation is applied in the periphery of the place field or 400–650 ms before the animals approached the center of the field. In summary, our data show that selective cholinergic activation triggers a robust network effect in the septo-hippocampal system during inactive behavioral state, whereas the non-cholinergic septal activation regulates hippocampal functional properties during explorative behavior. Together, our findings uncover fast septal modulation on hippocampal network and reveal how septal inputs up-regulate and down-regulate the encoding of spatial representation.

Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory

“…Cholinergic neuron activation can trigger the septohippocampal system during inactive behavioral states, whereas non-cholinergic septal cell activation regulates hippocampal function during explorative behavior (active states). Cholinergic neuron activity is, thus, necessary for the transition from inactive to active hippocampal-related behavior, but is inefficient in inducing significant change in the activity of the hippocampal neurons during arousal states (Mamad et al 2015). Moreover, optogenetic activation of septal cholinergic neurons increases hippocampal activity within the theta band (2-6 Hz) in anesthetized mice (Vandecasteele et al 2014), and exploratory tasks have been reported to increase AchC in hipoccampus (Roland et al 2014).…”

Efficacy of nonselective optogenetic control of the medial septum over hippocampal oscillations: the influence of speed and implications for cognitive enhancement

“…, ; Mamad et al. ; Tsanov ; Gangadharan et al. ) that ultimately provides the temporal framework for the coordinated suppression or facilitation of synaptic inputs (Csicsvari et al.…”

“…; Mamad et al. ) demonstrate the potential of this approach to serve as both a powerful tool for addressing fundamental basic science questions regarding the role of theta in learning and memory (Buzsaki ; Hasselmo ) and function as a neuroprosthetic that generates artificial oscillations in those with learning and memory difficulties. However, before researchers can address these possible uses of novel technology, there are two critical obstacles that must be addressed.…”

The Synergistic Enhancing-Memory Effect of Donepezil and S 38093 (a Histamine H3 Antagonist) Is Mediated by Increased Neural Activity in the Septo-hippocampal Circuitry in Middle-Aged Mice

“…Indeed, the medial septal area provides most of the cholinergic innervation of the hippocampus (Jakab and Septum, 1995; Mamad et al, 2015). …”