title: Vasopressin inhibits glutamate release via two distinct modes in the brainstem.
abstract: The hypothalamus coordinates autonomic responses in part through arginine vasopressin (AVP) released in medial nucleus tractus solitarius (NTS). However, the mechanisms and sites of AVP action within NTS pathways are uncertain. In brainstem slices, we activated solitary tract (ST) primary afferents to release glutamate and tested whether AVP modulated synaptic transmission to second-order neurons. NTS neurons were classified as second order by ST synaptic characteristics or the presence of anterograde tracers from peripheral baroreceptor afferents. Stimulus recruitment curves indicated ST-EPSCs on individual neurons were evoked by stimulation of single ST axons. Variance-mean (V-M) analysis of ST-EPSCs in individual neurons revealed uniformly high release probability (p approximately 0.9) from an average of 19 release sites (N) and a quantal size (q) of 34.0 +/- 4.7 pA. In 26 of 49 neurons, AVP inhibited afferent synaptic transmission. In most neurons, AVP reduced ST-EPSC amplitudes (n = 20) by decreasing p to 0.65, whereas q, N, and conduction times were unaffected. The V1a antagonist SR49059 alone decreased ST-EPSC V and increased M, suggesting tonic AVP actions, and blocked exogenous AVP action (n = 4). In other neurons with identical ST release properties, AVP induced synaptic failures and increased conduction time without altering the V-M relationship of successful ST-EPSCs (n = 6). Interestingly, frequency-depressed ST-EPSCs were not affected by AVP. AVP failed to alter holding or voltage-dependent potassium currents. Thus, AVP regulates NTS neurons by two distinct novel and state-dependent mechanisms: one, an analog, graded presynaptic inhibition of terminal glutamate release and the other, a binary, extraterminal block of conducted excitation.
authors.affiliation: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239-3098, USA. bailey.ohsu@gmail.com
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Bailey
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Jin
authors.forename: Mark W
authors.initials: MW
authors.lastname: Doyle
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Smith
authors.forename: Michael C
authors.initials: MC
authors.lastname: Andresen
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology / Q000502:physiology*; D004351:Drug Resistance; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D011311:Pressoreceptors / Q000187:drug effects; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000378:metabolism; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D018698:Glutamic Acid