title: The theta-related firing activity of parvalbumin-positive neurons in the medial septum-diagonal band of Broca complex and their response to 5-HT1A receptor stimulation in a rat model of Parkinson's disease.
abstract: The parvalbumin (PV)-positive neurons in the medial septum-diagonal band of Broca complex (MS-DB) play an important role in the generation of hippocampal theta rhythm involved in cognitive functions. These neurons in this region express a high density of 5-HT1A receptors which regulate the neuronal activity and consequently affect the theta rhythm. In this study, we examined changes in the theta-related firing activity of PV-positive neurons in the MS-DB, their response to 5-HT1A receptor stimulation and the corresponding hippocampal theta rhythm, and the density of PV-positive neurons and their co-localization with 5-HT1A receptors in rats with 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc). The lesion of the SNc decreased the rhythmically bursting activity of PV-positive neurons and the peak frequency of hippocampal theta rhythm. Systemic administration of 5-HT1A receptor agonist 8-OH-DPAT (0.5-128 µg/kg, i.v.) inhibited the firing rate of PV-positive neurons and disrupted rhythmically bursting activity of the neurons and the theta rhythm in sham-operated and the lesioned rats, respectively. The cumulative doses producing inhibition and disruption in the lesioned rats were higher than that of sham-operated rats. Furthermore, local application of 8-OH-DPAT (0.005 μg) in the MS-DB also inhibited the firing rate of PV-positive neurons and disrupted their rhythmically bursting activity in sham-operated rats, while having no effect on PV-positive neurons in the lesioned rats. The lesion of the SNc decreased the density of PV-positive neurons in the MS-DB, and percentage of PV-positive neurons expressing 5-HT1A receptors. These results indicate that the lesion of the SNc leads to suppression of PV-positive neurons in the MS-DB and hippocampal theta rhythm. Furthermore, the lesion decreases the response of these neurons to 5-HT1A receptor stimulation, which attributes to dysfunction and/or down-regulation of 5-HT1A receptor expression on these neurons. These changes may be involved in cognitive impairments of Parkinson's disease.
authors.affiliation: Department of Physiology and Pathophysiology, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Li
authors.forename: Ling-Na
authors.initials: LN
authors.lastname: Han
authors.forename: Qiao-Jun
authors.initials: QJ
authors.lastname: Zhang
authors.forename: Yi-Na
authors.initials: YN
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Feng
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D020667:Diagonal Band of Broca / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology*; D010320:Parvalbumins / Q000032:analysis*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000502:physiology; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects; D013826:Theta Rhythm / Q000187:drug effects / Q000502:physiology*
chemical_list: D010320:Parvalbumins; D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D016627:Oxidopamine; D001058:Apomorphine; D003891:Desipramine
keywords: 5-HT1A receptors; Parkinson's disease; hippocampal theta rhythm; medial septum-diagonal band of Broca complex; parvalbumin