Firing Properties of Anatomically Identified Neurons in the Medial Septum of Anesthetized and Unanesthetized Restrained Rats

Abstract

Cholinergic and GABAergic neurons in the medial septum-diagonal band of Broca (MS-DB) project to the hippocampus where they are involved in generating theta rhythmicity. So far, the functional properties of neurochemically identified MS-DB neurons are not fully characterized. In this study, MS-DB neurons recorded in urethane anesthetized rats and in unanesthetized restrained rats were labeled with neurobiotin and processed for immunohistochemistry against glutamic acid decarboxylase (GAD), parvalbumin (PV), and choline acetyltransferase (ChAT). The majority of the 90 labeled neurons (75.5%) were GADϩ. Among them, 34.0% were also PVϩ, but none were ChATϩ. Only 8.8% of the labeled neurons were found ChATϩ. Remaining neurons (15.5%) were not identified. In anesthetized rats, all of the PV/GADϩ and 65% of GADϩ neurons exhibited burst-firing activity at the theta frequency. PV/GADϩ neurons displayed higher discharge rate and longer burst duration compared with GADϩ neurons. At variance, all of the ChATϩ neurons were slow-firing. Cluster-firing and tonic-firing were observed in GADϩ and unidentified neurons. In unanesthetized rats, during wakefulness or rapid eye movement sleep with hippocampal theta, the bursting neurons were PV/GADϩ or GADϩ, whereas all of the ChATϩ neurons were slow-firing. Across the sleep-wake cycle, the GABAergic component of the septohippocampal pathway was always more active than the cholinergic one. The fact that cholinergic MS-DB neurons do not display theta-related bursting or tonic activity but have a very low firing rate questions how acetylcholine exerts its activating role in the septohippocampal system.

Social Interaction and Cocaine Conditioning in Mice Increase Spontaneous Spike Frequency in the Nucleus Accumbens or Septal Nuclei as Revealed by Multielectrode Array Recordings

“…The septal region can be divided into the lateral septum, containing mainly GABAergic neurons which coexpress calretinin or calbindin but not parvalbumin (PV) [25], and the medial septum. This contains GABAergic neurons (∼75% of total neurons), some coexpressing PV (∼35%), cholinergic neurons (∼9%) and glutamatergic neurons [26,27]. Both subregions are known to contain spontaneously active neurons, and in the medial septum, PV + GABAergic neurons have been found to be fast spiking [28,29].…”

Local Field Potentials: Myths and Misunderstandings

“…However, it would be more accurate to propose that a relationship exists between one structure and that which sets up the hippocampal theta, i.e., the medial septum. Thus, medial septal GABAergic neurons projecting to the hippocampus fire rhythmically at a theta frequency (Borhegyi et al, 2004; Simon et al, 2006) and they set-up theta LFPs there, either directly by activating synaptic currents or resonant properties in postsynaptic cells, or indirectly through interposed local interneurons (Colgin, 2013; Tsanov, 2015). In turn, most hippocampal projection cells, which generate the theta currents, become silent themselves during theta-related behavior, while only a few (place cells) fire transiently at a theta frequency.…”

Cholinergic modulation of hippocampal network function

“…Improved amperometric techniques now allow for the measurement of acetylcholine concentrations on faster sub-second timescales and have revealed that acetylcholine concentrations in the cortex can fluctuate rapidly with changes in behavioral state (Parikh et al, 2004, 2007; Burmeister et al, 2008; Mattinson et al, 2011; Howe et al, 2013; Paolone et al, 2013). Although acetylcholine concentrations appear to increase during theta oscillations in the hippocampus of anaesthetized rats, it is not clear whether the increase in hippocampal acetylcholine concentration is accompanied by an increase in firing of medial septal cholinergic neurons (Simon et al, 2006; Zhang et al, 2010, 2011) and whether this is tightly correlated with changes in oscillatory activity during the performance of hippocampal-dependent memory tasks.…”

“…Electrophysiologically, the neuronal cell types populating the medial septum have been classified as slow-firing (~5 Hz) cholinergic, fast- and burst-firing (~10–18 Hz) GABAergic and fast- and cluster-firing (~8–14 Hz) glutamatergic neurons (Griffith and Matthews, 1986; Markram and Segal, 1990b; Jones et al, 1999; Morris et al, 1999; Sotty et al, 2003; Simon et al, 2006; Huh et al, 2010). This classification is consistent with immunohistochemical data and reverse transcription-PCR analysis correlating electrophysiological properties with ChAT, glutamic acid decarboxylase 67 (GAD67) and vesicular glutamate transporters (VGLUT1, VGLUT2) mRNA expression (Sotty et al, 2003).…”