title: Glutamatergic drive facilitates synaptic inhibition of dorsal vagal motor neurons after experimentally induced diabetes in mice.
abstract: The role of central regulatory circuits in modulating diabetes-associated glucose dysregulation has only recently been under rigorous investigation. One brain region of interest is the dorsal motor nucleus of the vagus (DMV), which contains preganglionic parasympathetic motor neurons that regulate subdiaphragmatic visceral function. Previous research has demonstrated that glutamatergic and GABAergic neurotransmission are independently remodeled after chronic hyperglycemia/hypoinsulinemia. However, glutamatergic circuitry within the dorsal brain stem impinges on GABAergic regulation of the DMV. The present study investigated the role of glutamatergic neurotransmission in synaptic GABAergic control of DMV neurons after streptozotocin (STZ)-induced hyperglycemia/hypoinsulinemia by using electrophysiological recordings in vitro. The frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) was elevated in DMV neurons from STZ-treated mice. The effect was abolished in the presence of the ionotropic glutamate receptor blocker kynurenic acid or the sodium channel blocker tetrodotoxin, suggesting that after STZ-induced hyperglycemia/hypoinsulinemia, increased glutamatergic receptor activity occurs at a soma-dendritic location on local GABA neurons projecting to the DMV. Although sIPSCs in DMV neurons normally demonstrated considerable amplitude variability, this variability was significantly increased after STZ-induced hyperglycemia/hypoinsulinemia. The elevated amplitude variability was not related to changes in quantal release, but rather correlated with significantly elevated frequency of sIPSCs in these mice. Taken together, these findings suggest that GABAergic regulation of central vagal circuitry responsible for the regulation of energy homeostasis undergoes complex functional reorganization after several days of hyperglycemia/hypoinsulinemia, including both glutamate-dependent and -independent forms of plasticity.
authors.affiliation: Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky.
authors.forename: Carie R
authors.initials: CR
authors.lastname: Boychuk
authors.affiliation: Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky bret.smith@uky.edu.
authors.forename: Bret N
authors.initials: BN
authors.lastname: Smith
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D007736:Kynurenic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017470:Receptors, Glutamate / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D046509:Tissue Culture Techniques; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D007736:Kynurenic Acid
keywords: GABA; brain stem; diabetes; glutamate; synapse; vagus