Phase Segregation of Medial Septal GABAergic Neurons during Hippocampal Theta Activity

Abstract

Septo-hippocampal GABAergic neurons immunoreactive for parvalbumin are thought to play a crucial role in the generation of hippocampal theta oscillations associated with a specific stage of memory formation. Here we use in vivo juxtacellular recording and filling in the medial septum followed by immunocytochemical identification of the recorded cells containing parvalbumin to determine their firing pattern, phase relationship with hippocampal theta, morphology, and to thereby reveal their involvement in the generation of hippocampal theta activity. We have demonstrated that GABAergic medial septal neurons form two distinct populations exhibiting highly regular bursting activity that is tightly coupled to either the trough (178°) or the peak (330°) of hippocampal theta waves. Additionally, different types of bursting as well as nonbursting activity patterns were also observed. The morphological reconstruction of theta-bursting neurons revealed extensive axon arbors of these cells with numerous local collaterals establishing symmetrical synapses; thus, synchrony among the septal pacemaker units may be brought about by their recurrent collateral interactions. Long projecting axons could also be found running dorsally toward the hippocampus and ventrally in the direction of basal forebrain regions. We conclude that GABAergic neurons in the medial septum, which are known to selectively innervate hippocampal interneurons, are in a position to induce rhythmic disinhibition in the hippocampus and other theta-related subcortical areas at two different phases of hippocampal theta.

Hippocampal theta rhythm and its coupling with gamma oscillations require fast inhibition onto parvalbumin-positive interneurons

“…Inhibitory control of PVϩ interneurons has been suggested to be required for the generation of hippocampal theta rhythm (19,21,22,37). To test this hypothesis we recorded local field potentials (LFP) and unit activity in CA1 stratum pyramidale in behaving PV-⌬␥ 2 and control mice, using wire electrodes during exploration in an open field and sleep in a home cage.…”

GABAergic Neurons of the Medial Septum Lead the Hippocampal Network during Theta Activity

“…Thus, in this study, we investigated the following possible scenarios: (1) putative pacemaker MS neurons lead hippocampal field theta and hippocampal interneurons, proving a pacemaker role for the MS; (2) the activity changes of hippocampal interneurons precede those of MS cells, supporting the theory of hippocampal pacing of theta; (3) no significant temporal difference can be observed, which raises the possibility of a septal and a hippocampal pacemaker alternating or operating coincidentally, or a potential hidden pacemaker synchronizing the two areas. By implementing the circular statistical Z-shift method (Siapas et al, 2005), we demonstrated that alterations in the activity of the previously identified candidate pacemaker neurons (Borhegyi et al, 2004;Varga et al, 2008) in the MS precede those of putative hippocampal interneurons as well as corresponding changes in hippocampal field theta. Then, by using an information theoretical approach based on mutual information (MI) (Panzeri et al, 2007), we could show that the candidate pacemaker population of PV/HCN neurons share a higher amount of information with hippocampal theta than PV/HCN-immunonegative cells.…”

Nicotine induction of theta frequency oscillations in rodent medial septal diagonal band in vitro

“…Nicotine promotes oscillatory fi eld activity but not rhythmic burst fi ring in the MSDB in vitro The hippocampal theta rhythm in vivo is tied in which the presence of rhythmic burst firing activity recorded by extracellular electrodes in the midline regions of the MSDB [8,26] . Extrinsic, non-cortical inputs to the septum seem to control the incidence of the burst fi ring [7][8][9] , but there has been controversy as to whether this activity in the MSDB is generated intrinsically by tonic input or is driven by theta-patterned input from elsewhere, most notably the SUM [6] .…”