Involvement of GABAergic and cholinergic medial septal neurons in hippocampal theta rhythm

Hippocampus. 2005;15(3):381-92. doi: 10.1002/hipo.20062.


Hippocampal theta rhythm (HPCtheta) may be important for various phenomena, including attention and acquisition of sensory information. Two types of HPCtheta (types I and II) exist based on pharmacological, behavioral, and electrophysiological characteristics. Both types occur during locomotion, whereas only type II (atropine-sensitive) is present under urethane anesthesia. The circuit of HPCtheta synchronization includes the medial septum-diagonal band of Broca (MSDB), with cholinergic and gamma-aminobutyric acid (GABA)ergic neurons comprising the two main projections from MSDB to HPC. The primary aim of the present study was to assess the effects of GABAergic MSDB lesions on urethane- and locomotion-related HPCtheta, and compare these effects to those of cholinergic MSDB lesions. Saline, kainic acid (KA), or 192 IgG-saporin (SAP) was injected into MSDB before recording. KA preferentially destroys GABAergic MSDB neurons, whereas SAP selectively eliminates cholinergic MSDB neurons. A fixed recording electrode was placed in the dentate mid-molecular layer, and stimulating electrodes were placed in the posterior hypothalamus (PH), and medial perforant path (PP). Under urethane anesthesia, HPCtheta was induced by tail pinch, PH stimulation, and systemic physostigmine; none of the rats with KA or SAP showed HPCtheta in any of these conditions. During locomotion, HPCtheta was attenuated, but not eliminated, in rats with KA or SAP lesions. Intraseptal KA in combination with either intraseptal SAP or PP lesions reduced locomotion-related HPCtheta beyond that observed with each lesion alone, virtually eliminating HPCtheta. In contrast, intraseptal SAP combined with PP lesions did not reduce HPCtheta beyond the effect of each lesion alone. We conclude that both GABAergic and cholinergic MSDB neurons are necessary for HPCtheta under urethane, and that each of these septohippocampal projections contributes to HPCtheta during locomotion.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / metabolism*
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Anesthetics, Intravenous
  • Animals
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / metabolism
  • Denervation
  • Electric Stimulation
  • Female
  • Fornix, Brain / drug effects
  • Fornix, Brain / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Locomotion / physiology
  • Male
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurotoxins
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Septal Nuclei / drug effects
  • Septal Nuclei / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Theta Rhythm / drug effects*
  • Urethane / pharmacology
  • gamma-Aminobutyric Acid / metabolism*


  • Anesthetics, Intravenous
  • Neurotoxins
  • Urethane
  • gamma-Aminobutyric Acid
  • Acetylcholine