Modulation of septo-hippocampal θ activity by GABAA receptors: an experimental and computational approach1
Section snippets
Animals
All studies were conducted with male Sprague–Dawley rats (270–300 g; Harlan, Indianapolis, IN, USA). Animals were housed in groups of four, kept under conditions of controlled temperature (21±1 °C) and lighting (lights on 06:00–18:00 h) and were given food pellets and water ad libitum. Studies were performed between 8:00 and 17:00 h. All procedures were carried out under an approved animal use protocol and were in compliance with the Animal Welfare Act Regulations (9 CFR Parts 1, 2 and 3) and
In vivo electrophysiology of the septo-hippocampal system
Activity of MS/DB neurons recorded from anesthetized rats showed a considerable variability in their activity and firing pattern. The mean firing rate of MS/DB neurons calculated during the control period was 19.4±3.7 spikes/s (n=17), ranging from 0.4 to 50.3 spikes/s. As it has been previously established (Bland et al., 1999, Ford et al., 1989, Vertes and Kocsis, 1997), firing pattern of MS/DB neurons was directly related to hippocampal EEG activity, showing oscillation during hippocampal θ
Discussion
The present findings demonstrate that systemic administration of the anxiolytic diazepam, a positive allosteric modulator of GABAA receptors inhibits, whereas the anxiogenic FG-7142, a negative allosteric modulator of GABAA receptors enhances θ activity of the septo-hippocampal system. Responses of the septo-hippocampal system observed in pharmacological experiments are mirrored by our computational septo-hippocampal model, at both neuronal and circuitry levels, when the actions of allosteric
Acknowledgements
This work was supported by grants from the OTKA (T038140) and the OMFB (IKTA-00064/2003 KPI), the Henry R. Luce Foundation and a research grant from Pharmacia/Pfizer.
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2013, Experimental NeurologyCitation Excerpt :Studies on animals showed that MSDB neurons exhibit a rhythmic burst-firing activity, which is phase-locked to hippocampal theta oscillations (Alonso et al., 1987; Bland and Colom, 1993; Dutar et al., 1986; Gogolak et al., 1967; Green and Аrduini, 1954; Petsche et al., 1962; Stewart and Fox, 1990; Sweeney et al., 1992) and can maintain their rhythmic bursting activity in the absence of hippocampal theta rhythm (e.g., after hippocampal seizures or pharmacological treatment) (Petsche et al., 1962). To characterize a specific role of septal bursting cells and their relation to the hippocampal theta rhythm, their activity has been intensively studied in vivo (Barrenechea et al., 1995; Bassant et al., 1995; Brazhnik and Fox, 1999; Colom et al., 2006; Hajós et al., 2004; King, et al., 1998; Kitchigina and Butuzova, 2009; Lee et al., 1994; Manseau et al., 2005) and also in vitro in the complete septohippocampal preparations (Goutagny et al., 2008; Huh et al., 2010; Manseau et al., 2008) and septal slices (Henderson and Jones, 2005; Henderson et al., 2001; Lu et al., 2011; Malkov and Popova, 2011a; Mal'kov et al., 2008). It has been revealed that the occurrence of hippocampal theta oscillations depends on the proportion of septal neurons involved in the rhythmic process; the theta-frequency of septal bursts determines the frequency of theta field activity in hippocampus (Bland et al. 1999; Vertes and Kocsis, 1997; Vinogradova 1995).
FG7142, yohimbine, and βcCE produce anxiogenic-like effects in the elevated plus-maze but do not affect brainstem activated hippocampal theta
2013, NeuropharmacologyCitation Excerpt :Our results clearly show that none of FG7142, yohimbine or βCCE had any positive modulatory effect on evoked hippocampal theta frequency. Interestingly, Hajós et al. (2004) found that FG7142 (1 mg/kg) enhanced the firing rate and theta rhythmicity of medial septal/diagonal band neurons and induced an increase in the power of spontaneous theta in chloral hydrate anesthetized rats. In addition, they also found that FG7142 could reverse the inhibition of the above measures induced by diazepam.
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Supplementary data associated with this article can be found at doi:10.1016/j.neuroscience.2004.03.043.