Abstract
This study explored the effects of septal glutamatergic transmission on septal-hippocampal theta activity via intraseptal microinjection of antagonist at AMPA receptors (AMPAR). The current results showed that microinjection of AMPAR antagonist, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione, 20 μg/μl, 0.5 μl), evoked a decrease in the frequency of theta activity evoked by various means in anesthetized and behaving rat. Theta wave activity was induced on: (a) intraseptal microinjection of carbachol, an agonist at cholinergic receptors, (b) reticular stimulation, (c) exploration in novel open field (OF), and (d) hind paw (HP) injection of the algogen, formalin. The effect on frequency in the formalin test was observed in an early period on injection of formalin, which was novel to the animal, but not in the later more sustained phase of the formalin test. The effect of NBQX, being seen in both anesthetized and behaving animals, suggests that the modulation of theta wave frequency, including in novelty, is a function of AMPAR in MS. The effect of the antagonist on theta power was less apparent, being observed only in anesthetized animals. In addition to theta power and frequency, intraseptal NBQX also attenuated suppression of CA1 population spike (PS) induced by intraseptal carbachol, thus suggesting that septal glutamate neurotransmission is involved in the spectrum of MS-mediated network responses. Indeed, in the context of behavior, formalin injection induced an increase in the level of septal glutamate, while NBQX attenuated nociceptive behaviors. Notably, MS is involved in the modulation of formalin nociception. These findings suggest that AMPA receptors are a key modulator of septal physiological function.
Highlights
The onset and offset of animal nociceptive behavior, i.e., flinching and licking were marked onto Spike2 during the formalin test
The rostral pontine oralis nucleus (RPO)-induced theta wave activity and suppression of population spike (PS) are mediated through the hypothalamic supramammillary nucleus (SuM) and involve the medial septal region (MS) (Jiang and Khanna, 2004; Ariffin et al, 2010)
The analysis revealed that pre-treatment with Vehicle or NBQX10 had no significant effect on duration of amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) induced theta activity (Figures 4A,C; Vehicle; time × treatment: F22, 231 = 0.8856, P = 0.6141; NBQX10; time × treatment: F22, 231 = 0.7376, P = 0.7981)
Summary
The medial septal region (MS) is implicated in various aspects of behavior such as affect-motivation, cognition, behavioral arousal, and sensorimotor integration (Winson, 1978; Gray, 1982; Bland, 1986, 2009; Givens and Olton, 1990; Nagahara and McGaugh, 1992; Gray and McNaughton, 2000; Bland and Oddie, 2001; Ma et al, 2002; Glutamate Modulation of Septo-HippocampusMcNaughton and Corr, 2004; McNaughton et al, 2006; Shin et al, 2009; Ang et al, 2015, 2017; Wang et al, 2015). The medial septal region (MS) is implicated in various aspects of behavior such as affect-motivation, cognition, behavioral arousal, and sensorimotor integration The septal glutamatergic neuropil and intraseptal glutamatergic transmission have been proposed to affect a wide range of septo-hippocampal functions, including theta activation, sensorimotor behaviors, PH, and cognition (Elvander-Tottie et al, 2006; Fuhrmann et al, 2015; Ariffin et al, 2018). While there is evidence of AMPAR-mediated nociceptive process in experimental neuropathic pain (Ariffin et al, 2018), there is a lack of information on its role in acute nociception within the septohippocampal network
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