The medial septum mediates impairment of prepulse inhibition of acoustic startle induced by a hippocampal seizure or phencyclidine.

Abstract

The involvement of the septohippocampal system on the impaired sensorimotor gating induced by phencyclidine (PCP) or by an electrically induced hippocampal seizure was examined in behaving rats. An impaired sensorimotor gating, measured by prepulse inhibition (PPI) of the acoustic startle response, was observed following a hippocampal afterdischarge (AD) or systemic injection of PCP and was accompanied with an increase in hippocampal gamma waves (30-70 Hz). The medial septum infusion with muscimol (0.25 microg), a GABA(A) receptor agonist, 15 min prior to PCP or a hippocampal AD, prevented the impairment of sensorimotor gating and the increase in gamma waves. By itself, muscimol (0.25 microg) injection into the medial septum did not affect PPI, although it significantly suppressed spontaneous gamma waves. In order to identify subpopulations of neurons mediating the sensorimotor gating deficit and the hippocampal gamma wave increase, 0.14-0.21 microg of p75 antibody conjugated to saporin (192 IgG-saporin) was injected into the medial septum to selectively lesion the septohippocampal cholinergic neurons. Neither the PPI deficit nor the gamma wave increase induced by PCP or a hippocampal AD was affected by 192 IgG-saporin lesion of the medial septum. It is concluded that increase in neural activity in the medial septum participates in the impairment of sensorimotor gating and the increase in hippocampal gamma waves induced by PCP or a hippocampal AD. It is suggested that the GABAergic but not the cholinergic septohippocampal neurons mediate the sensorimotor gating deficit.

• Authors: Jingyi Ma, Bixia Shen, N Rajakumar, L Stan Leung
• Journal: Behavioural brain research (Behav Brain Res) Vol. 155 Issue 1 Pg. 153-66 (Nov 05 2004) ISSN: 0166-4328 [Print] Netherlands
• PMID: 15325789 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 192 IgG-saporin
• Antibodies, Monoclonal
• Cholinergic Agents
• Excitatory Amino Acid Antagonists
• GABA Agonists
• Immunotoxins
• Parvalbumins
• Ribosome Inactivating Proteins, Type 1
• Muscimol
• Choline O-Acetyltransferase
• N-Glycosyl Hydrolases
• Saporins
• Phencyclidine

Topics

• Animals
• Antibodies, Monoclonal (toxicity)
• Behavior, Animal
• Brain Injuries (physiopathology)
• Cell Count (methods)
• Choline O-Acetyltransferase (metabolism)
• Cholinergic Agents (toxicity)
• Dose-Response Relationship, Drug
• Dose-Response Relationship, Radiation
• Drug Interactions
• Electric Stimulation (adverse effects)
• Electroencephalography
• Excitatory Amino Acid Antagonists (toxicity)
• GABA Agonists (pharmacology)
• Hippocampus (injuries, metabolism, physiopathology, radiation effects)
• Immunohistochemistry (methods)
• Immunotoxins (toxicity)
• Male
• Muscimol (pharmacology)
• N-Glycosyl Hydrolases
• Neural Inhibition (drug effects, physiology, radiation effects)
• Parvalbumins (metabolism)
• Phencyclidine (toxicity)
• Rats
• Rats, Long-Evans
• Reflex, Acoustic (drug effects, physiology)
• Ribosome Inactivating Proteins, Type 1
• Saporins
• Seizures (etiology, physiopathology)
• Septum Pellucidum (drug effects, physiology)