The theta‐related firing activity of parvalbumin‐positive neurons in the medial septum‐diagonal band of broca complex and their response to 5‐HT_1A 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.

Local and Distant Input Controlling Excitation in Layer II of the Medial Entorhinal Cortex

“…We tested how inhibition via PV + long-range projections affected the activity of targeted FS neurons. We depolarized responding FS cells to suprathreshold potentials and activated long-range axons locally with 8-Hz laser pulses of 60-ms duration to simulate rhythmic burst firing of PV + cells in the MS ( Borhegyi et al., 2004 , King et al., 1998 , Li et al., 2014 ). All analyzed FS neurons in MEC LII reduced their firing rate during laser stimulation transiently (n = 11 cells from 5 mice; Figure 7 F).…”

Brainstem system of hippocampal theta induction: The role of the ventral tegmental area

“…If inactivating injection of 6‐OHDA was located precisely in the VTA, theta frequency decreased in EEG during PS (Sei et al ). Also complete unilateral 6‐hydroxydopamine lesions of the medial forebrain bundle decreased peak frequency of hippocampal theta rhythm (Li‐Bo et al, ). Conversely, there is strong evidence that the VTA affects theta rhythm mainly by modulating its amplitude.…”

Low intensity repetitive transcranial magnetic stimulation modulates brain-wide functional connectivity to promote anti-correlated c-Fos expression

“…The magnitude of anticorrelated functional connectivity is dampened in several conditions, including depression 51,52 , Parkinson's disease 53 , stroke 54 , and anxiety 55 . These same conditions have also been demonstrated to have altered parvalbumin interneuron activity [56][57][58][59] . Many of the symptoms of these conditions have also been shown to improve with rTMS treatment [60][61][62][63] .…”