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GABA and Glycine are Co‐released into Dorsal Motor Nucleus of the Vagus Neurons following a Perinatal High Fat Diet
Author(s) -
Clyburn Courtney Elizabeth,
Browning Kirsteen N.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.861.9
Subject(s) - glycine receptor , gabaergic , inhibitory postsynaptic potential , dorsal motor nucleus , neuroscience , gabaa receptor , postsynaptic current , postsynaptic potential , bicuculline , neurotransmission , chemistry , biology , glycine , receptor , vagus nerve , excitatory postsynaptic potential , biochemistry , stimulation , amino acid
Efferent motoneurons of the adult dorsal motor nucleus of the vagus (DMV) have previously been shown to only receive GABAergic inhibitory synaptic inputs. In contrast, it has been demonstrated that, at early postnatal time points, motoneurons of the DMV receive both GABAergic and glycinergic inhibitory synaptic inputs. The developmental decline in glycinergic input has been determined to occur in the second postnatal week. Our previous work has suggested that rats that are fed a perinatal high fat diet (pHFD) do not undergo this developmental shift and maintain a glycinergic input into adulthood. The purpose of this study was to test the hypothesis that glycine and GABA are co‐released from the same synaptic terminal in pHFD rats. Whole cell patch clamp recordings were made from DMV neurons in pHFD or control fed Sprague‐Dawley rats 4–6 weeks of age. These rats were fed either a control chow or HFD (14 or 60%kcal from fat, respectively) from embryonic day 13. The effects of the benzodiazepines (BZD) clonazepam (100nM), an allosteric modulator of the a2/3 subunit containing GABA A receptor, and zolpidem (1μM) an allosteric modulator of the a1 subunit containing GABA A receptor, on miniature postsynaptic inhibitory currents (mIPSCs) were examined. Application of BZDs is known to modulate the open probability of ligand‐gated GABA A , but not glycine, ion channels, thus increasing the decay of the slower GABAergic, but not the faster glycinergic mIPSCs. This allows for the differentiation of mixed concurrent glycinergic and GABAergic currents through the identification of two distinct rates of decay. Application of clonazepam significantly increased the proportion of two‐phased mIPSCs in the DMV of pHFD rats (76/200 vs 14/213 n=6 neurons, p<0.05), but not in controls (10/156 vs 11/164, n=6 neurons, p>0.05). Similarly, application of zolpidem significantly increased the proportion of two‐phased mIPSCs in the DMV of pHFD rats (60/179 vs and 14/153, n=6, p<0.05) but not in controls (27/150 vs and 8/138, n=5, p>0.05). This study confirms our previous studies suggesting that exposure to a pHFD prevents the developmental decline in glycinergic currents onto the DMV neurons and further suggests that glycine and GABA are co‐released from the same synaptic terminal. Furthermore, significant differences were not apparent between the effects of zolpidem and clonazepam, suggesting that a1, 2 and 3 receptor subunits form functional GABA A receptors in pHFD DMV neurons. These developmental alternations in inhibitory signaling in brainstem motoneurons may result in the dysregulation of gastrointestinal reflexes and gastric motility observed in these rats. Support or Funding Information Funded by NIH 078364 and NSF IOS1148978