Activation of Group II Metabotropic Glutamate Receptors Suppresses Excitability of Mouse Main Olfactory Bulb External Tufted and Mitral Cells

Abstract

Metabotropic glutamate receptors (mGluRs) are abundantly expressed in the rodent main olfactory bulb. The function of Group I mGluRs has been investigated in a number of studies, while the actions of Group II mGluRs, which include the mGluR2 and mGluR3 subtypes, have been less well explored. Here, we used electrophysiological approaches in mouse olfactory bulb slices to investigate how Group II mGluR activation and inactivation modifies the activity of external tufted (ET) and mitral cells. The Group II mGluR agonist DCG-IV was found to directly and uniformly reduce the spontaneous discharge of ET and mitral cells. The inhibitory effect of DCG-IV was absent in mitral cells with truncated apical dendrites, indicating a glomerular site of action. DCG-IV did not influence olfactory nerve-evoked monosynaptic responses in ET or mitral cells, indicating that Group II mGluRs do not presynaptically modulate glutamate release from olfactory nerve terminals. In contrast, DCG-IV suppressed polysynaptic responses in periglomerular cells evoked by olfactory nerve stimulation. DCG-IV also inhibited glutamate release from ET cells, and suppressed the spontaneous and olfactory nerve-evoked long-lasting depolarization in mitral cells. Applied alone, Group II receptor antagonists were without effect, suggesting that basal activation of these receptors is nil. These findings suggest that Group II mGluRs inhibit ET and mitral cell activity and further dampen intraglomerular excitatory circuits by suppressing glutamate release.

AgRP/NPY Neuron Excitability Is Modulated by Metabotropic Glutamate Receptor 1 During Fasting

“…Once isolated, DHPG perfusion results in slow excitatory currents (Figure 6B ) in a subset of AgRP/NPY neurons ( n = 4/16; Figure 6C ). The slow current observed occurs over the timescale of minutes as previously described under previous measurements of mGluR1 induced slow current (Heinbockel et al, 2004 ; Dong and Ennis, 2018 ). The average amplitude of observed slow currents is greater than 10 pA (Figure 6D ), which is a physiologically relevant influence on small neurons such as AgRP/NPY neurons (Baver et al, 2014 ).…”

“…Consistent with visual evidence for localization of mGluR1 on AgRP/NPY neurons and the observed change in firing rate, we report functional post-synaptic effects of DHPG directly on AgRP/NPY neurons. Voltage clamp electrophysiology revealed a DHPG-induced slow excitatory post-synaptic current in a subset of AgRP/NPY neurons of fasted mice under ionotropic synaptic blockade, similar to the slow-current observed in cells in the olfactory bulb (Heinbockel et al, 2004 ; Dong and Ennis, 2018 ). Given reports that a 10 pA change to the rheobase of small neurons like AgRP/NPY neurons can result in substantial changes to their level of activation (Baver et al, 2014 ), our observed change demonstrates a physiologically relevant slow current which can influence excitability of AgRP/NPY neurons.…”

Circuit contributions to sensory-driven glutamatergic drive of olfactory bulb mitral and tufted cells during odorant inhalation

“…This effect is consistent with a disinhibition of glutamatergic drive by APV+NBQX, and could reflect the removal of feedback presynaptic inhibition of OSN terminals (Wachowiak et al, 2005;Shao et al, 2009) or blockade of feedforward inhibition of ET cells; GABAB receptor blockade using CGP35348 prior to APV+NBQX application, as we did with low-frequency inhalations, should distinguish these possibilities. Lastly, we did not attempt to block metabotropic glutamate receptors in these experiments, although they have been implicated in diverse contributions to MT cell and ET cell excitability, including mediating prolonged odorant-evoked MT cell responses in vivo (Dong and Ennis, 2014;Dong and Ennis, 2017;Matsumoto et al, 2009). Despite the need for further dissection of the transmitter pathways involved in glomerular processing, our results suggest that multisynaptic circuits may contribute more to slow temporal patterning of glutamatergic drive to MT cells than to shaping inhalation-linked excitatory dynamics.…”

Parallel multimodal circuits control an innate foraging behavior

“…The net effect of mgl-1 is to inhibit its target neurons, AIA and ADE, but animals with and without mgl-1 generate AIA calcium transients, suggesting that mgl-1 does not eliminate neuronal excitability. mgl-1 encodes a Group II metabotropic receptor (Dillon et al, 2006), whose mammalian homologs inhibit neurotransmitter release (Dong and Ennis, 2017;Hayashi et al, 1993); therefore mgl-1 may decrease the synaptic output of AIA and ADE. In agreement with this possibility, inhibition of AIA or ADE synaptic release with tetanus toxin can substitute for mgl-1 action in local search behavior ( Fig.…”