Ketamine-induced Deficit of Auditory Gating in the Hippocampus of Rats is Alleviated by Medial Septal Inactivation and Antipsychotic Drugs

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2009 Aug 6

PMID 19655127

Citations 7

Authors

Jingyi Ma

Siew Kian Tai

L Stan Leung

Affiliations

Soon will be listed here.

Abstract

Rationale: Gating of sensory responses is impaired in schizophrenic patients and animal models of schizophrenia. Ketamine, an N-methyl-D-aspartate receptor antagonist, is known to induce schizophrenic-like symptoms including sensory gating deficits in humans.

Objective: This study aims to investigate the mechanisms underlying ketamine's effect on gating of auditory evoked potentials in the hippocampus of freely moving rats.

Methods: Gating was measured by the ratio of the test-click response (T) to the conditioning-click response (C), or T/C, with T and C measured as peak amplitudes.

Results: Ketamine (1, 3, or 6 mg/kg s.c.) injection dose-dependently increased T/C ratio as compared to saline injection (s.c.). T/C ratio was 0.48 +/- 0.05 after saline injection and 0.73 +/- 0.17 after ketamine (3 mg/kg s.c.) injection. The increase in T/C ratio after ketamine was blocked by prior inactivation of the medial septum with GABA(A) receptor agonist muscimol or by systemic administration of antipsychotic drugs, including chlorpromazine (5 mg/kg i.p.), haloperidol (1 mg/kg i.p.), or clozapine (7.5 mg/kg i.p.). Infusion of muscimol into the medial septum or injection of an antipsychotic drug alone did not affect the T/C ratio. However, rats with selective lesion of the septohippocampal cholinergic neurons by 192 IgG-saporin showed a significantly higher T/C ratio (0.86 +/- 0.10) than sham lesion rats (0.26 +/- 0.07), and ketamine did not further increase T/C ratio in rats with septohippocampal cholinergic neuron lesion.

Conclusions: Ketamine's disruption of hippocampal auditory gating was normalized by inactivation of the medial septum; in addition, septal cholinergic neurons participate in normal auditory gating.

Citing Articles

The Consciousness of Pain: A Thalamocortical Perspective.

Sgourdou P NeuroSci. 2024; 3(2):311-320.

PMID: 39483367 PMC: 11523681. DOI: 10.3390/neurosci3020022.

Medial Septum Modulates Consciousness and Psychosis-Related Behaviors Through Hippocampal Gamma Activity.

Leung L, Ma J Front Neural Circuits. 2022; 16:895000.

PMID: 35874429 PMC: 9301478. DOI: 10.3389/fncir.2022.895000.

The Medial Septum as a Potential Target for Treating Brain Disorders Associated With Oscillopathies.

Takeuchi Y, Nagy A, Barcsai L, Li Q, Ohsawa M, Mizuseki K Front Neural Circuits. 2021; 15:701080.

PMID: 34305537 PMC: 8297467. DOI: 10.3389/fncir.2021.701080.

Effects of GABA-B receptor positive modulator on ketamine-induced psychosis-relevant behaviors and hippocampal electrical activity in freely moving rats.

Ma J, Leung L Psychopharmacology (Berl). 2017; 234(20):3129-3142.

PMID: 28756462 DOI: 10.1007/s00213-017-4705-7.

Dual Effects of Limbic Seizures on Psychosis-Relevant Behaviors Shown by Nucleus Accumbens Kindling in Rats.

Ma J, Leung L Brain Stimul. 2016; 9(5):762-769.

PMID: 27267861 PMC: 4980124. DOI: 10.1016/j.brs.2016.05.006.

References

Leung L . Spectral analysis of hippocampal EEG in the freely moving rat: effects of centrally active drugs and relations to evoked potentials. Electroencephalogr Clin Neurophysiol. 1985; 60(1):65-77. DOI: 10.1016/0013-4694(85)90952-6. View

Duncan G, Miyamoto S, Leipzig J, Lieberman J . Comparison of brain metabolic activity patterns induced by ketamine, MK-801 and amphetamine in rats: support for NMDA receptor involvement in responses to subanesthetic dose of ketamine. Brain Res. 1999; 843(1-2):171-83. DOI: 10.1016/s0006-8993(99)01776-x. View

Hajos N, Papp E, Acsady L, Levey A, Freund T . Distinct interneuron types express m2 muscarinic receptor immunoreactivity on their dendrites or axon terminals in the hippocampus. Neuroscience. 1998; 82(2):355-76. DOI: 10.1016/s0306-4522(97)00300-x. View

Fitch T, Sahr R, Eastwood B, Zhou F, Yang C . Dopamine D1/5 receptor modulation of firing rate and bidirectional theta burst firing in medial septal/vertical limb of diagonal band neurons in vivo. J Neurophysiol. 2006; 95(5):2808-20. DOI: 10.1152/jn.01210.2005. View

Bickford P, Freedman R . Cholinergic gating of response to auditory stimuli in rat hippocampus. Brain Res. 1992; 587(1):130-6. DOI: 10.1016/0006-8993(92)91437-j. View

Ehrlichman R, Gandal M, Maxwell C, Lazarewicz M, Finkel L, Contreras D . N-methyl-d-aspartic acid receptor antagonist-induced frequency oscillations in mice recreate pattern of electrophysiological deficits in schizophrenia. Neuroscience. 2008; 158(2):705-12. DOI: 10.1016/j.neuroscience.2008.10.031. View

Ma J, Leung L . The supramammillo-septal-hippocampal pathway mediates sensorimotor gating impairment and hyperlocomotion induced by MK-801 and ketamine in rats. Psychopharmacology (Berl). 2007; 191(4):961-74. DOI: 10.1007/s00213-006-0667-x. View

Lee S, Wynn J, Green M, Kim H, Lee K, Nam M . Quantitative EEG and low resolution electromagnetic tomography (LORETA) imaging of patients with persistent auditory hallucinations. Schizophr Res. 2006; 83(2-3):111-9. DOI: 10.1016/j.schres.2005.11.025. View

Ma J, Brudzynski S, Leung L . Involvement of the nucleus accumbens-ventral pallidal pathway in postictal behavior induced by a hippocampal afterdischarge in rats. Brain Res. 1996; 739(1-2):26-35. DOI: 10.1016/s0006-8993(96)00793-7. View

10.

Miller C, Freedman R . Medial septal neuron activity in relation to an auditory sensory gating paradigm. Neuroscience. 1993; 55(2):373-80. DOI: 10.1016/0306-4522(93)90506-b. View

11.

Adler L, Pachtman E, Franks R, Pecevich M, Waldo M, Freedman R . Neurophysiological evidence for a defect in neuronal mechanisms involved in sensory gating in schizophrenia. Biol Psychiatry. 1982; 17(6):639-54. View

12.

Nagamoto H, Johnson R, Adler L, Egan M, Rose G, Freedman R . Auditory sensory gating in hippocampal neurons: a model system in the rat. Biol Psychiatry. 1990; 27(2):183-92. DOI: 10.1016/0006-3223(90)90648-l. View

13.

Gao B, Hornung J, Fritschy J . Identification of distinct GABAA-receptor subtypes in cholinergic and parvalbumin-positive neurons of the rat and marmoset medial septum-diagonal band complex. Neuroscience. 1995; 65(1):101-17. DOI: 10.1016/0306-4522(94)00480-s. View

14.

Herrmann C, Demiralp T . Human EEG gamma oscillations in neuropsychiatric disorders. Clin Neurophysiol. 2005; 116(12):2719-33. DOI: 10.1016/j.clinph.2005.07.007. View

15.

Kelly P, Iversen S . Selective 6OHDA-induced destruction of mesolimbic dopamine neurons: abolition of psychostimulant-induced locomotor activity in rats. Eur J Pharmacol. 1976; 40(1):45-56. DOI: 10.1016/0014-2999(76)90352-6. View

16.

Moxon K, Gerhardt G, Gulinello M, Adler L . Inhibitory control of sensory gating in a computer model of the CA3 region of the hippocampus. Biol Cybern. 2003; 88(4):247-64. PMC: 4170679. DOI: 10.1007/s00422-002-0373-7. View

17.

Leung L, Shen B . Long-term potentiation at the apical and basal dendritic synapses of CA1 after local stimulation in behaving rats. J Neurophysiol. 1995; 73(5):1938-46. DOI: 10.1152/jn.1995.73.5.1938. View

18.

Jirsa R, Poc P, Radil T . Hippocampal auditory evoked response threshold in the rat: behavioral modulation. Brain Res Bull. 1992; 28(2):149-53. DOI: 10.1016/0361-9230(92)90173-u. View

19.

de Bruin N, Ellenbroek B, van Luijtelaar E, Cools A, Stevens K . Hippocampal and cortical sensory gating in rats: effects of quinpirole microinjections in nucleus accumbens core and shell. Neuroscience. 2001; 105(1):169-80. DOI: 10.1016/s0306-4522(01)00183-x. View

20.

Grunze H, Rainnie D, Hasselmo M, Barkai E, Hearn E, McCarley R . NMDA-dependent modulation of CA1 local circuit inhibition. J Neurosci. 1996; 16(6):2034-43. PMC: 6578507. View