Parabrachial Nucleus Of The Pons Research Articles

Spontaneous Changes in Taste Sensitivity of Single Units Recorded over Consecutive Days in the Brainstem of the Awake Rat.

A neuron’s sensitivity profile is fundamental to functional classification of cell types, and underlies theories of sensory coding. Here we show that gustatory neurons in the nucleus of the solitary tract (NTS) and parabrachial nucleus of the pons (PbN) of awake rats spontaneously change their tuning properties across days. Rats were surgically implanted with a chronic microwire assembly into the NTS or PbN. Following recovery, water-deprived rats had free access to a lick spout that delivered taste stimuli while cellular activity was recorded. In 12 rats for the NTS and 8 rats for the PbN, single units could be isolated at the same electrode on consecutive days (NTS, 14 units for 2–5 consecutive days, median = 2 days; PbN, 23 units for 2–7 days, median = 2.5 days). Waveforms were highly similar (waveform template correlation > 0.99) across days in 13 units in NTS and 13 units in PbN. This degree of similarity was rare (0.3% of pairs in NTS, 1.5% of pairs in PbN) when the waveforms were from presumed-different neurons (units recorded on nonconsecutive days with at least one intervening day in which there were no spikes, or from different wires or rats). Analyses of multi-day recordings that met this criterion for “same unit” showed that responses to taste stimuli appeared, disappeared, or shifted in magnitude across days, resulting in changes in tuning. These data imply, generally, that frameworks for cell classification and, specifically, that theories of taste coding, need to consider plasticity of response profiles.

Taste coding in the parabrachial nucleus of the pons in awake, freely licking rats and comparison with the nucleus of the solitary tract

In the rodent, the parabrachial nucleus of the pons (PbN) receives information about taste directly from the nucleus of the solitary tract (NTS). Here we examined how information about taste quality (sweet, sour, salty, and bitter) is conveyed in the PbN of awake, freely licking rats, with a focus on how this information is transformed from the incoming NTS signals. Awake rats with electrodes in the PbN had free access to a lick spout that delivered taste stimuli (5 consecutive licks; 100 mM NaCl, 10 mM citric acid, 0.01 mM quinine HCl, or 100 mM sucrose and water) or water (as a rinse) on a variable-ratio schedule. To assess temporal coding, a family of metrics that quantifies the similarity of two spike trains in terms of spike count and spike timing was used. PbN neurons (n = 49) were generally broadly tuned across taste qualities with variable response latencies. Some PbN neurons were quiescent during lick bouts, and others, some taste responsive, showed time-locked firing to the lick pattern. Compared with NTS neurons, spike timing played a larger role in signaling taste in the first 2 s of the response, contributing significantly in 78% (38/49) of PbN cells compared with 45% of NTS cells. Also, information from temporal coding increased at a faster rate as the response unfolded over time in PbN compared with NTS. Collectively, these data suggest that taste-related information from NTS converges in the PbN to enable a subset of PbN cells to carry a larger information load.

Temporal coding of taste in the parabrachial nucleus of the pons of the rat

Recent studies have provided evidence that temporal coding contributes significantly to encoding taste stimuli at the first central relay for taste, the nucleus of the solitary tract (NTS). However, it is not known whether this coding mechanism is also used at the next synapse in the central taste pathway, the parabrachial nucleus of the pons (PbN). In the present study, electrophysiological responses to taste stimuli (sucrose, NaCl, HCl, and quinine) were recorded from 44 cells in the PbN of anesthetized rats. In 29 cells, the contribution of the temporal characteristics of the response to the discrimination of various taste qualities was assessed. A family of metrics that quantifies the similarity of two spike trains in terms of spike count and spike timing was used. Results showed that spike timing in 14 PbN cells (48%) conveyed a significant amount of information about taste quality, beyond what could be conveyed by spike count alone. In another 14 cells (48%), the rate envelope (time course) of the response contributed significantly more information than spike count alone. Across cells there was a significant correlation (r = 0.51; P < 0.01) between breadth of tuning and the proportion of information conveyed by temporal dynamics. Comparison with previous data from the NTS (Di Lorenzo PM and Victor JD. J Neurophysiol 90: 1418-31, 2003 and J Neurophysiol 97: 1857-1861, 2007) showed that temporal coding in the NTS occurred in a similar proportion of cells and contributed a similar fraction of the total information at the same average level of temporal precision, even though trial-to-trial variability was higher in the PbN than in the NTS. These data suggest that information about taste quality conveyed by the temporal characteristics of evoked responses is transmitted with high fidelity from the NTS to the PbN.

Water as an Independent Taste Modality

To qualify as a “basic” taste quality or modality, defined as a group of chemicals that taste alike, three empirical benchmarks have commonly been used. The first is that a candidate group of tastants must have a dedicated transduction mechanism in the peripheral nervous system. The second is that the tastants evoke physiological responses in dedicated afferent taste nerves innervating the oropharyngeal cavity. Last, the taste stimuli evoke activity in central gustatory neurons, some of which may respond only to that group of tastants. Here we argue that water may also be an independent taste modality. This argument is based on the identification of a water dedicated transduction mechanism in the peripheral nervous system, water responsive fibers of the peripheral taste nerves and the observation of water responsive neurons in all gustatory regions within the central nervous system. We have described electrophysiological responses from single neurons in nucleus of the solitary tract (NTS) and parabrachial nucleus of the pons, respectively the first two central relay nuclei in the rodent brainstem, to water presented as a taste stimulus in anesthetized rats. Responses to water were in some cases as robust as responses to other taste qualities and sometimes occurred in the absence of responses to other tastants. Both excitatory and inhibitory responses were observed. Also, the temporal features of the water response resembled those of other taste responses. We argue that water may constitute an independent taste modality that is processed by dedicated neural channels at all levels of the gustatory neuraxis. Water-dedicated neurons in the brainstem may constitute key elements in the regulatory system for fluid in the body, i.e., thirst, and as part of the swallowing reflex circuitry.

Information Processing in the Parabrachial Nucleus of the Pons

As the second synapse in the central gustatory pathway of the rodent, the parabrachial nucleus of the pons (PbN) receives information about taste stimuli directly from the nucleus of the solitary tract (NTS). Data show that NTS cells amplify taste responses before transmitting taste-related signals to the PbN. NTS cells of varied response profiles send converging input to PbN cells, though input from NTS cells with similar profiles is more effective at driving PbN responses. PbN cells follow NTS input for the first 3 s of taste stimulation for NaCl, HCl, and quinine, but are driven in cyclic bursts throughout the response interval for sucrose. Analyses of the temporal characteristics of NTS and PbN responses show that both structures use temporal coding with equal effectiveness to identify taste quality. Thus, the NTS input to the PbN is comprehensive, in that PbN cells receive NTS input that could support broad sensitivity, systematic, in that the time course of PbN firing patterns depend reliably on the tastant, and efficient, in that information from the NTS is preserved as it is communicated across structures. Comparisons of NTS and PbN taste responses in rats form the basis for our speculation that in primates, where the central gustatory pathway does not synapse in the PbN, the function of the PbN in taste processing may have been incorporated into that of the NTS.

A naloxonazine sensitive (μ 1 receptor) mechanism in the parabrachial nucleus modulates eating

The parabrachial nucleus (PBN) is an area of the brain stem that controls eating and contains endogenous opioids and their receptors. Previously, we demonstrated that acute activation of μ opioid receptors (MOPR) in the lateral PBN increased food consumption. MOPRs have been divided operationally into μ 1 and μ 2 receptor subtypes on the basis of the ability of naloxonazine (Nlxz) to block the former but not the latter. We used autoradiography to measure whether Nlxz blocks stimulation by the μ 1/μ 2 agonist DAMGO (D-Ala2, N-Me-Phe4, Gly5-ol-enkephalin) of the incorporation of [ 35S]-guanosine 5′(γ-thio)triphosphate ([ 35S]-GTPγS) into sections of the PBN. In vitro, Nlxz dose dependently inhibited receptor coupling in all areas of the PBN. The 1 μM concentration of Nlxz reduced stimulation by 93.1 ± 5% in the lateral inferior PBN (LPBNi) and by 90.5 ± 4% in the medial parabrachial subregion (MPBN). Administration of Nlxz directly into the LPBNi decreased both food intake and agonist stimulated coupling, ex vivo, for the 24-h period after infusion. Infusion of Nlxz into the intended area reduced food intake by 42.3% below baseline values. Nlxz infusion prevented DAMGO stimulation of G-protein coupling in LPBNi and markedly reduced this stimulation in the MPBN. The incomplete inhibition of DAMGO-stimulated coupling in the MPBN is most likely due to the limited diffusion of Nlxz from the site of infusion (LPBNi) into this brain region. In conclusion, this study demonstrates that the μ 1 opioid receptor subtype is present in the parabrachial nucleus of the pons and that these receptors serve to modulate feeding in rats.

Transfer of information about taste from the nucleus of the solitary tract to the parabrachial nucleus of the pons

In the study of the neural code for gustation, the relative sensitivity of a cell to a variety of taste stimuli is defined as its response profile. To study the construction of response profiles from incoming signals, electrophysiological responses to NaCl, HCl, quinine-HCl, sucrose and Na saccharin were recorded simultaneously in pairs of single cells: one in the nucleus of the solitary tract (NTS) and the other in the parabrachial nucleus of the pons (PbN), respectively the first and second synapses in the central pathway for gustation. Of 37 units recorded in the NTS and 32 in the PbN, 12 (32%) pairs showed evidence of functional connectivity. Although PbN responses were significantly larger than those in the NTS in general, no amplification of NTS activity was apparent among those units that were functionally connected. Analysis of NTS–PbN connectivity patterns suggests that PbN units receive input from NTS units with response profiles that are both similar and different from their own pattern of sensitivities. Further analysis suggests that the stimulus-selectivity of the response profile of a PbN unit may be determined by stimulus-selective input from NTS cells that show similar response profiles. However, input from NTS cells with response profiles different from their own appears to be non-stimulus-selective. Analysis of the organization of response profiles in the two structures suggests that the cells in both the NTS and PbN cannot be easily distinguished by their patterns of sensitivity to taste stimuli.

Prostaglandin-H synthase-1 (PGHS-1) gene is expressed in specific neurons of the brain of the late gestation ovine fetus

Prostaglandin (PG) E 2 acts on the brain stem to modulate breathing activity in the ovine fetus. The source of this PGE 2 is unknown and we hypothesized that it is produced locally in the developing brain and functions in a paracrine and/or autocrine manner. The purpose of the present study was to establish whether prostaglandin-H synthase-1 (PGHS-1), a crucial enzyme in de novo prostaglandin synthesis, is present and its gene expressed in the ovine fetal brain. Immunohistochemical and molecular hybridization techniques were used to identify sites of PGHS-1 immunoreactivity and PGHS-1 mRNA expression respectively in the brain of the ovine fetus in late gestation (approximately 126 days gestation, term 145 days). PGHS-1 immunoreactivity was localized to specific regions of the fetal brain, including the cortex, hypothalamus, hippocampal formation, superior colliculus of the midbrain, parabrachial nucleus of the pons, and the reticular formation, raphe, nucleus of the solitary tract, and gracile and cuneate nuclei of the medulla. The relative abundance of PGHS-1 mRNA in selected brain regions, as determined by Northern blot analysis, correlated qualitatively with the number of PGHS-1 immunoreactive neurons identified in each region. In situ hybridization demonstrated PGHS-1 mRNA to be localized in the same neurons or nuclei as PGHS-1 immunoreactivity. These results indicate that PGHS-1 is synthesized de novo in many brain regions including two that are important in respiratory control: the pneumotaxic center (parabrachial nucleus) and the dorsal respiratory group (nucleus tractus solitarius) suggesting that prostaglandins that modulate fetal respiratory activity are synthesized endogenously.

Corticofugal influence on taste responses in the nucleus of the solitary tract in the rat.

1. Previous work has revealed a pervasive influence of the gustatory neocortex (GN) on the electrophysiological responses to taste in the parabrachial nucleus of the pons (PbN), the second synapse in the central pathway for gustation. Subsequent experiments have further suggested that direct projections from the GN to the PbN are not sufficiently dense to account for the widespread effects of cortical input. Because the main source of input to the PbN, i.e., the nucleus of the solitary tract (NTS), also receives input from the GN, the present experiment was conducted to test the hypothesis that changes in taste responses in the PbN after temporary elimination of GN input may be a normal reaction to altered input originating in the NTS. 2. Fourty-three taste-responsive neurons in the NTS were isolated initially in urethan-anesthetized rats. Single units were then classified as "relay" (n = 12) or "nonrelay" (n = 13) on the basis of their electrophysiological response to electrical shocks delivered to the taste-responsive portion of the PbN. After histological analyses, 18 units were classified as "unknown" because the PbN stimulating electrode was found to be outside the anatomically defined taste area in the pons. 3. Electrophysiological responses to sapid solutions of the NaCl (0.1 M), HCl (0.01 M), quinineHCl (0.01 M), sucrose (0.5 M), and Na-saccharin (0.004 M) were then recorded before and after recovery from infusions of procaineHCl into the GN. Both the ipsilateral and contralateral sides of the GN, in that order, received procaine infusions separated by a recovery period of at least 45 min. 4. Analysis of across-unit patterns of response was accomplished with the use of a vector space analysis. With this approach, the response of a given neuron to a given tastant is considered as a coordinate in n-dimensional space, where n is the number of neurons tested. The responses to each stimulus generate vectors whose length relates to the overall magnitude of response across the sample and whose relative directionality indicates similarity to other across-unit patterns. Measures derived from this type of analysis were used as input in a multidimensional scaling (MDS) analysis designed to summarize the organization of the across-unit patterns of response generated by the taste stimuli. This type of analysis creates a "taste space" in which similar across-unit patterns of response are placed close together and dissimilar patterns are placed far apart.(ABSTRACT TRUNCATED AT 400 WORDS)

Taste responses in neurons in the nucleus of the solitary tract that do and do not project to the parabrachial pons.

1. Mechanisms of neural coding of gustatory stimuli were studied in the nucleus of the solitary tract (NTS), the first relay in the neural pathway for gustation, in anesthetized rats. Taste-responsive NTS units were identified as "relay" or "nonrelay" based on the electrophysiological response to electrical pulses delivered to the parabrachial nucleus of the pons (PbN), the second relay in the neural pathway for gustation. Coding mechanisms in each group were analyzed separately. 2. Taste responses to sapid solutions of NaCl (0.1 M), HCl (0.01 M), quinine HCl (0.01 M), sucrose (0.5 M) and Na-saccharin (0.004 M) were recorded in single units in the NTS. After gustatory stimulation, electrophysiological responses to electrical stimulation of the taste-responsive part of the ipsilateral PbN were recorded. A 0.2-ms pulse was delivered at 75-250 microA at a rates of 1, 25, 50 and 100 pps through a bipolar stainless steel electrode. An antidromic response was defined as a time-locked spike that occurred at a fixed latency after PbN stimulation that followed high stimulation frequencies. A collision test also was performed. 3. Of 42 taste-responsive NTS units, 19 (45%) were relay units, 22 (52%) were nonrelay and 1 unit was activated orthodromically by PbN stimulation. Latencies of evoked spikes ranged from 1.75 to 4.0 ms 2.1 +/- 0.2 ms (mean +/- SE, median, 1.75 ms). 4. Examination of general response characteristics revealed few differences among relay and nonrelay units.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticofugal input to taste-responsive units in the parabrachial pons

Taste responses in units in the parabrachial nucleus of the pons (PbN) that receive direct projections from the gustatory neocortex (GN) were examined in the rat. Electrical stimulation was applied to the GN with bipolar stimulating electrodes. Time-locked responses to GN stimulation were observed in 19 of 62 (31%) taste-responsive units identified in the PbN. Of these, 17 units produced excitatory responses following GN stimulation and 2 units showed evidence of inhibition. No evidence of antidromic activation of PbN units was apparent. These results are consistent with descriptions of the anatomical projections from the GN to the PbN and demonstrate that some portion of taste-responsive neural elements within the PbN receive direct cortical input. PbN units that followed GN stimulation could not be distinguished from those that did not follow either by their spontaneous rates or their response profiles. These results suggest that axons from the GN do not select targets within the PbN based on the particular response properties.

Taste responses in the parabrachial pons of ovariectomized rats

Since the early 1970s it has been known that female rats prefer higher concentrations of sweet stimuli compared with males. Recent data have revealed that electrophysiological responses to sweet tastes recorded in the parabrachial nucleus of the pons (PbN), the second relay in the neural pathway for taste, are larger in diestrous female rats compared with those in males. Because it has been shown that ovariectomized rats have lowered preferences for saccharin compared with intact females, it is possible to predict that responses to sweet stimuli in the PbN of ovariectomized rats might be smaller than those in intact females. To investigate this hypothesis, electrophysiological responses to representatives of the 4 basic taste qualities i.e., salty, sour, sweet and bitter, were recorded in the PbN of ovariectomized rats. Gustatory stimuli included NaCl (0.1 M), HCl (0.01 M), sucrose (0.5 M), quinine HCl (0.01 M) and Na-saccharin (0.004 M). Comparison of taste responses of 49 PbN units in ovariectomized rats with those in the PbN of intact female and male rats showed that responses to sweet stimuli were of comparable magnitude to those in female rats but elevated compared with those in male rats. However, responses of PbN units to quinine appeared to be larger in ovariectomized rats compared with those in the PbN of both intact female and male rats. These results suggest that decreased saccharin preference in ovariectomized rats may reflect a greater sensitivity to the bitter components of the taste of saccharin. Moreover, these data provide evidence that taste responses in the PbN are influenced by both the activational and organizational actions of ovarian hormones.

Corticofugal influence on taste responses in the parabrachial pons of the rat

Although the anatomy of centrifugal input to gustatory neural structures has been described, little is known of the physiological mechanisms that convey this influence or of their functional significance. As a first step in the investigation of these issues, the effect of a reversible lesion in the gustatory neocortex (GN) on the neural code for taste in the parabrachial nucleus of the pons (PbN) was studied in rats. Electrophysiological responses to taste stimuli bathed over the tongue were recorded from single units in the PbN before, after and following recovery from an infusion of procaine-HCl into the GN. Test stimuli consisted of sapid solutions of NaCl (0.1 M), HCl (0.01 M), sucrose (0.5 M), Na-saccharin (0.004 M) and quinine-HCl (0.01 M). Infusions of procaine into the GN were correlated with both specific and nonspecific effects on the responsitivity to gustatory stimuli in the PbN. Specific effects included: (1) changes in the magnitude of response to some tastants, but not others, in a given PbN unit, (2) changes in the across unit patterns produced by sweet stimuli and (3) the appearance of OFF responses in a subset of PbN units. Nonspecific effects were evidenced by changes in the spontaneous rates of activity and by enhancement or suppression of responses across all the tastantts tested in a subset of PbN units. Comparison of these results with reports on the effects of decerebration suggests that some of these effects may be accounted for by interruption of the descending input from the GN to the PbN. In addition, the stimulus-specific effects that were noted following procaine infusion into the GN provide support for the suggestion that the GN specifically modifies the electrophysiological patterns that are evoked by salient taste stimuli.

Taste responses in the parabrachial pons of male, female and pregnant rats

Sex-related and pregnancy-related variations in taste preferences have long been known to exist in humans as well as animals. However, the neurophysiological underpinnings of these variations have not yet been described. In an effort to discover whether differences in hormonal state are reflected in the neural processing within the gustatory system, electrophysiological responses to representatives of the 4 basic taste qualities were recorded in the parabrachial nucleus of the pons (PbN) of male, diestrous female and pregnant rats. Results revealed that PbN units in female and pregnant rats showed larger responses to sweet stimuli than units in male rats. Also, a greater proportion of units in female and pregnant rats were classified as sweet-best compared with units in males. This result may correlate with the greater preference for sweet stimuli in female rats compared with males that has been reported in the behavioral literature. Analysis of response profiles with multidimensional scaling techniques showed that units that responded best to a given stimulus were placed near that stimulus for units from males, but not for units from female and pregnant rats. Hierarchical cluster analysis of response profiles suggested 3 clusters of units within each group of PbN units. Response profiles within clusters showed different types of units in male, female and pregnant rats. Collectively, these data suggest that ovarian hormones may act to alter the central processing of gustatory information. Evidence for both activational and organizational effects of ovarian hormones on the gustatory system is discussed.

Evidence for corticotropin‐releasing factor, neurotensin, and somatostatin in the neural pathway from the central nucleus of the amygdala to the parabrachial nucleus

The central nucleus of the amygdala (CNA) and the parabrachial nucleus of the pons (PBN) are included within a group of brain nuclei involved in autonomic responses. Previous studies have shown that the CNA sends a considerable projection to the PBN and that both nuclei contain neurons immunoreactive to many different peptides. In the present study, we used the combined retrograde fluorescence-immunofluorescence method to determine whether the CNA projection to the PBN contains any of the following neuropeptides: corticotropin-releasing factor (CRF), neurotensin (NT), somatostatin (SS), and enkephalin (ENK). Following injections of fluorescent dye into the PBN, neurons within both lateral and medial subdivisions of the CNA were retrogradely labeled. A significant percentage of CRF (54-66%)-, NT (40-53%)-, and SS (31-50%)-immunoreactive neurons were retrogradely labeled, predominantly within the lateral CNA. Enkephalin-immunoreactive neurons were never retrogradely labeled, although they were often found adjacent to retrogradely labeled neurons. Our results show that the lateral CNA is a major source of CRF, NT, and SS terminals within the PBN. Neurons in the medial CNA also provide a significant contribution to the CNA-PBN pathway, but their chemical nature remains to be determined. We conclude that CRF, NT, and SS are important putative neurotransmitters in the CNA's regulation of PBN function. This CNA-PBN peptidergic pathway may participate in stress-related cardiovascular and respiratory responses.