Cranial primary afferents from the viscera enter the brain at the solitary tract nucleus (NTS), where their information is integrated for homeostatic reflexes. The organization of sensory inputs is poorly understood, despite its critical impact on overall reflex performance characteristics. Single afferents from the solitary tract (ST) branch within NTS and make multiple contacts onto individual neurons. Many neurons receive more than one ST input. To assess the potential interaction between converging afferents and proximal branching near to second-order neurons, we probed near the recorded soma in horizontal slices from rats with focal electrodes and minimal shocks. Remote ST shocks evoked monosynaptic excitatory postsynaptic currents (EPSCs), and nearby focal shocks also activated monosynaptic EPSCs. We tested the timing and order of stimulation to determine whether focal shocks influenced ST responses and vice versa in single neurons. Focal-evoked EPSC response profiles closely resembled ST-EPSC characteristics. Mean synaptic jitters, failure rates, depression, and phenotypic segregation by capsaicin responsiveness were indistinguishable between focal and ST-evoked EPSCs. ST-EPSCs failed to affect focal-EPSCs within neurons, indicating that release sites and synaptic terminals were functionally independent and isolated from cross talk or neurotransmitter overflow. In only one instance, focal shocks intercepted and depleted the ST axon generating evoked EPSCs. Despite large numbers of functional contacts, multiple afferents do not appear to interact, and ST axon branches may be limited to close to the soma. Thus single or multiple primary afferents and their presynaptic active release sites act independently when they contact single second-order NTS neurons.
In the present study, we have examined neurochemical correlates that may be involved in the differential cardiovascular responses observed in normotensive and hypertensive rats during stress. Using a restraint stress paradigm, both normotensive Wistar Kyoto (WKY) and Spontaneously Hypertensive rats (SHR) underwent acute (1 h restraint in a perspex tube), chronic (1 h restraint for ten consecutive days) or no restraint (control) stress. Following cessation of restraint, rats were processed by incubating sections of brain stem and kidney 125 125 1 8 with ( I)-HO-LVA (0.03 nM) or ( I)Sar Ile -AngiotensinII (0.5 nM), in the presence of PD123319 (10 mM) or losartan (10 mM), to determine the distribution and density of vasopressin V , angiotensin AT and AT receptors, respectively. Analysis of autoradiograms 1A 1 2 indicated changes in the density of radioligand binding in acutely and chronically-stressed rats, as compared to controls. For example, V1A binding in the medial nucleus tractus solitarius (SolM) decreased in the WKY but increased in the SHR. AT binding in SolM did not 1 significantly change in the WKY but decreased in the SHR with repeated restraint. In kidney slices, AT binding decreased with stress in 1 the WKY (217%) but increased in SHR (110-15%). AT binding in the kidney showed a pattern similar to that of AT binding in SHR, 2 1 but not WKY. Graded increases in V binding were measured in kidney medulla and cortex of both strains (150-60% with chronic 1A restraint). These results suggest that physiological adaptation to restraint is associated with specific changes in V , AT and AT receptor 1A 1 2
Cranial visceral primary afferents follow the solitary tract (ST) to synapse on 2 nd order NTS neurons. These afferents consist of both A‐fibers (transient receptor potential vanilloid receptor negative (TRPV1 − )) and C‐fibers (TRPV1 + ). The inhibitory transmitter GABA acts ionotropically at GABA A and metabotropically at GABA B receptors. In horizontal hindbrain slices, ST shocks evoked time‐invariant glutamatergic EPSCs with jitters <200 μs at 2 nd order neurons. Capsaicin (TRPV1 + agonist) blocked C‐fiber afferent transmission. We tested whether the GABA B agonist, baclofen (BAC), reduces glutamate release of TRPV1 + afferents on 2 nd order NTS neurons. During GABA A block with gabazine, BAC (0.001–20 μM) reduced ST‐EPSC amplitudes and rates of sEPSCs or mEPSCs (in TTX), consistent with presynaptic decreases in glutamate release. BAC effects were more pronounced in 1 mM (physiological) than 2 mM bath calcium, consistent with masking effects of increased probability of glutamate release in high calcium. These data are consistent with presynaptic GABA B control of glutamate release at C‐fiber afferent terminals. Future studies will test whether BAC reduces glutamate release at TRPV1 − synapses. Supported by: HL‐088894 (JHP) and HL‐04119 (MCA)
Abstract Chemogenetic activation of oxytocin receptor‐expressing neurons in the parabrachial nucleus (Oxtr PBN neurons) acts as a satiation signal for water. In this research, we investigated the effect of activating Oxtr PBN neurons on satiation for different types of fluids. Chemogenetic activation of Oxtr PBN neurons in male and female transgenic Oxtr Cre mice robustly suppressed the rapid, initial (15‐min) intake of several solutions after dehydration: water, sucrose, ethanol and saccharin, but only slightly decreased intake of Ensure®, a highly caloric solution (1 kcal/mL; containing 3.72 g protein, 3.27 g fat, 13.42 g carbohydrates, and 1.01 g dietary fibre per 100 mL). Oxtr PBN neuron activation also suppressed cumulative, longer‐term (2‐h) intake of lower caloric, less palatable solutions, but not highly caloric, palatable solutions. These results suggest that Oxtr PBN neurons predominantly control initial fluid‐satiation responses after rehydration, but not longer‐term intake of highly caloric, palatable solutions. The suppression of fluid intake was not because of anxiogenesis, but because Oxtr PBN neuron activation decreased anxiety‐like behaviour. To investigate the role of different PBN subdivisions on the intake of different solutions, we examined FOS as a proxy marker of PBN neuron activation. Different PBN subdivisions were activated by different solutions: the dorsolateral PBN similarly by all fluids; the external lateral PBN by caloric but not non‐caloric solutions; and the central lateral PBN primarily by highly palatable solutions, suggesting PBN subdivisions regulate different aspects of fluid intake. To explore the possible mechanisms underlying the minimal suppression of Ensure® after Oxtr PBN neuron activation, we demonstrated in in vitro slice recordings that the feeding‐associated agouti‐related peptide (AgRP) inhibited Oxtr PBN neuron firing in a concentration‐related manner, suggesting possible inhibition by feeding‐related neurocircuitry of fluid satiation neurocircuitry. Overall, this research suggests that although palatable beverages like sucrose‐ and ethanol‐containing beverages activate fluid satiation signals encoded by Oxtr PBN neurons, these neurons can be inhibited by hunger‐related signals (agouti‐related peptide, AgRP), which may explain why these fluids are often consumed in excess of what is required for fluid satiation.
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