Abstract
The medial habenula (MHb) plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal. The MHb receives GABAergic input from the medial septum/diagonal band of Broca (MS/DB), yet the synaptic mechanism that regulates MHb activity is unclear. GABA (γ -aminobutyric acid) is a major inhibitory neurotransmitter activating both GABAA receptors and GABAB receptors. Depending on intracellular chloride concentration, however, GABAA receptors also function in an excitatory manner. In the absence of various synaptic inputs, we found that MHb neurons displayed spontaneous tonic firing at a rate of about ~4.4 Hz. Optogenetic stimulation of MS/DB inputs to the MHb evoked GABAA receptor-mediated synaptic currents, which produced stimulus-locked neuronal firing. Subsequent delayed yet lasting activation of GABAB receptors attenuated the intrinsic tonic firing. Consequently, septal GABAergic input alone orchestrates both excitatory GABAA and inhibitory GABAB receptors, thereby entraining the firing of MHb neurons.
Highlights
The medial habenula (MHb) plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal[1,2,3]
In the present study, exploiting the optogenetic controls of medial septum/diagonal band of Broca (MS/DB) input to the MHb, we showed that GABA released from MS/DB afferents entrains MHb neuronal firing by orchestrating both excitatory GABAA receptors and inhibitory GABAB receptors
We have demonstrated functional GABAergic synaptic connectivity between the MS/DB and the MHb
Summary
The MHb plays an important role in nicotine-related behaviors such as nicotine aversion and withdrawal[1,2,3]. Neurons in the ventral two-thirds of the MHb comprise cholinergic subdivision of the nucleus: These neurons densely express cholineacetyltranferase (ChAT) and nicotinic acetylcholine receptors[4,5]. They exhibit spontaneous tonic firings that are not synchronized with other adjacent neurons[4]. GABA is known to inhibit neuronal activity via both GABAA and GABAB receptors. In the present study, exploiting the optogenetic controls of MS/DB input to the MHb, we showed that GABA released from MS/DB afferents entrains MHb neuronal firing by orchestrating both excitatory GABAA receptors and inhibitory GABAB receptors
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