Causal relationships between neurons of the nucleus incertus and the hippocampal theta activity in the rat

Abstract

In recent years, a body of evidence has shown that the nucleus incertus (NI), in the dorsal tegmental pons, is a key node of the brainstem circuitry involved in hippocampal theta rhythmicity. Ascending reticular brainstem system activation evokes hippocampal theta rhythm with coupled neuronal activity in the NI. In a recent paper, we showed three populations of neurons in the NI with differential firing during hippocampal theta activation. The objective of this work was to better evaluate the causal relationship between the activity of NI neurons and the hippocampus during theta activation in order to further understand the role of the NI in the theta network. A Granger causality analysis was run to determine whether hippocampal theta activity with sensory-evoked theta depends on the neuronal activity of the NI, or vice versa. The analysis showed causal interdependence between the NI and the hippocampus during theta activity, whose directional flow depended on the different neuronal assemblies of the NI. Whereas type I and II NI neurons mainly acted as receptors of hippocampal information, type III neuronal activity was the predominant source of flow between the NI and the hippocampus in theta states. We further determined that the electrical activation of the NI was able to reset hippocampal waves with enhanced theta-band power, depending on the septal area. Collectively, these data suggest that hippocampal theta oscillations after sensory activation show dependence on NI neuron activity, which could play a key role in establishing optimal conditions for memory encoding.

GABAergic Neurons in the Rat Medial Septal Complex Express Relaxin-3 Receptor (RXFP3) mRNA

“…Moreover, infusion of a Rln3 analog into the MS increased hippocampal theta rhythm, whereas infusion of a Rln3 receptor antagonist impaired the theta rhythm produced by novel environment exploration or RPO stimulation ( Ma et al, 2009 ). Different approaches in recent years have confirmed and extended these observations regarding the role of the NI and its associated peptide Rln3 in subcortical modulation of hippocampal theta rhythm, with an observed synchrony between the firing of NI neurons and different phases of hippocampal theta rhythm ( Ma et al, 2013 ; Martínez-Bellver et al, 2015 , 2017 ).…”

Chronic activation of the relaxin‐3 receptor on GABA neurons in rat ventral hippocampus promotes anxiety and social avoidance

“…Therefore, in the future, it will be of interest to determine which SST/GABA and PV/GABA neuron populations are altered by endogenous RXFP3 signaling and how this underlies different behavioral states. It will also be important to further assess the effect of RXFP3 activation on the neurophysiological activity of the hippocampus under conditions such as the home cage and in tests of anxiety or social interaction, including recordings of local field potentials and hippocampal theta (Klausberger et al, , ), since suppression of hippocampal theta is a well‐established feature of anxiolytic agents, while its elevation is associated with anxiety; and recent evidence confirms a strong association between a major group of relaxin‐3 neurons in the NI and likely relaxin‐3/RXFP3‐mediated modulation of hippocampal theta (Ma & Gundlach, ; Ma, Shen, Sang, Lanciego, & Gundlach, ; Ma et al, ; Martínez‐Bellver et al, ).…”

Mapping Cell Types and Efferent Pathways in the Ascending Relaxin-3 System of the Nucleus Incertus

“…In the neocortex, fibers were prominent in the infralimbic (IL) and dorsal peduncular (DP) areas ( Figure 8A,B), and in the retrosplenial cortex (RS, Figure 8C,D,F,G). Functional studies of the NI have focused on its input to the septohippocampal system (Martinez-Bellver et al, 2015;Martinez-Bellver et al, 2017;Szőnyi et al, 2019;Lu et al, 2020). In the hippocampus, labelled fibers were prominent in CA3, and sparse in CA1, and lacking in the dentate gyrus (DG, Figure 8C,D,F,G).…”