Medial Septal GABAergic Neurons Express the Somatostatin sst_2AReceptor: Functional Consequences on Unit Firing and Hippocampal Theta

Abstract

GABAergic septohippocampal neurons play a major role in the generation of hippocampal theta rhythm, but modulatory factors intervening in this function are poorly documented. The neuropeptide somatostatin (SST) may be one of these factors, because nearly all hippocampal GABAergic neurons projecting to the medial septum/diagonal band of Broca (MS-DB) express SST. In this study, we took advantage of the high and selective expression of the SST receptor sst 2A in MS-DB to examine its possible role on theta-related activity. Immunohistochemical experiments demonstrated that sst 2A receptors were selectively targeted to the somatodendritic domain of neurons expressing the GABAergic marker GAD67 but were not expressed by cholinergic neurons. In addition, a subpopulation of GABAergic septohippocampal projecting neurons expressing parvalbumin (PV) also displayed sst 2A receptors. Using in vivo juxtacellular recording and labeling with neurobiotin, we showed that a number of bursting and nonbursting neurons exhibiting high discharge rates and brief spikes were immunoreactive for PV or GAD67 and expressed the sst 2A receptor. Microiontophoresis applications of SST and the sst 2A agonist octreotide (OCT) showed that sst 2A receptor activation decreased the discharge rate of both nonbursting and bursting MS-DB neurons and lessened the rhythmic activity of the latter. Finally, intraseptal injections of OCT and SST in freely moving rats reduced the power of hippocampal EEG in the theta band. Together, these in vivo experiments suggest that SST action on MS-DB GABAergic neurons, through sst 2A receptors, represents an important modulatory mechanism in the control of theta activity.

Distribution and targets of the relaxin‐3 innervation of the septal area in the rat

“…The distribution pattern of GAD67 positive neurons we observed in the medial septum was similar to that described by (Bassant et al, 2005).…”

“…Indeed, such studies are the goal of our current and future research (e.g. Ma et al, 2009b;Bassant et al, 2005;Simon et al, 2006).…”

β‐adrenergic receptors are differentially expressed in distinct interneuron subtypes in the rat hippocampus

“…The primary antibodies used in this study were the following: rabbit polyclonal antibodies against ␤1 adrenergic receptor (Jane-wit et al, 2007) and ␤2 adrenergic receptor (Guo and Li, 2007); mouse monoclonal antibodies against calretinin (Lagace et al, 2007), calbindin (Celio, 1990), cholecystokinin (Pawelzik, 2002), and parvalbumin (Celio, 1990); sheep polyclonal antibody against neuropeptide Y (Jinno and Kosaka, 2006); and goat polyclonal antibody against somatostatin (Bassant et al, 2005). Further details regarding each of the primary antibodies used in this study are given below and in Table 1.…”

Firing Properties of Anatomically Identified Neurons in the Medial Septum of Anesthetized and Unanesthetized Restrained Rats

“…Using juxtacellular recording and labeling with neurobiotin, it was shown that PV immunoreactive (PVϩ) neurons exhibited bursting activity tightly coupled to hippocampal theta waves (Borhegyi et al, 2004;Bassant et al, 2005). RB activity was also observed in GABAergic neurons found to express glutamic acid decarboxylase (GAD) but not PV (Bassant et al, 2005). These data demonstrated undoubtedly that the GABAergic MS-DB neurons are capable of displaying bursting activity at theta frequency.…”

“…Numerous in vivo studies attempted to establish the nature of the RB septal neurons, but, until recently, the correlation between neurochemical phenotypes and firing properties remained indirect. Using juxtacellular recording and labeling with neurobiotin, it was shown that PV immunoreactive (PVϩ) neurons exhibited bursting activity tightly coupled to hippocampal theta waves (Borhegyi et al, 2004;Bassant et al, 2005). RB activity was also observed in GABAergic neurons found to express glutamic acid decarboxylase (GAD) but not PV (Bassant et al, 2005).…”