Joseph B. Travers

Motor and premotor mechanisms of licking.

The location, organization and anatomical connections of a central pattern generator (CPG) for licking are discussed. Anatomical and physiological studies suggest a brainstem location distributed within several subdivisions of the medullary reticular formation (RF). The involvement of widespread RF regions is evident from brainstem recording experiments in awake freely moving preparations and studies employing electrical stimulation of the frontal cortex to produce ororhythmic activity. The complex multifunctional properties of RF neurons producing licking are indicated by their activity during licking, swallowing and the rejection of an aversive gustatory stimulus. Anatomical studies place descending inputs to a brainstem CPG for licking to widely distributed areas of both the medial and lateral RF. In contrast, most projections originating from brainstem orosensory nuclei terminate primarily within the lateral RF. Because many pre-oromotor neurons appear concentrated largely in the intermediate zone of the RF (IRt), it is hypothesized that neurons from both lateral and medial sites converge within the IRt to control oromotor function.

Ascending and descending projections from the rostral nucleus of the solitary tract originate from separate neuronal populations

Anterograde studies have shown that neurons within the rostral (gustatory) nucleus of the solitary tract project to the parabrachial nucleus, as well as to sites within the medulla including the reticular formation and caudal nucleus of the solitary tract. In order to determine the degree to which the same neurons contribute to both projections, injections of retrograde tracers were made simultaneously into both the parabrachial nuclei and medullary reticular formation of the rat. Only a small proportion of neurons were double labeled. Consistent with studies in hamster, labeled neurons projecting to the parabrachial nuclei in rat consisted of both stellate and elongate neurons, concentrated within the central subdivision of the rostral nucleus of the solitary tract. Injections into the medullary reticular formation also labeled both stellate and elongate neurons but these were concentrated in the ventral subdivision of the nucleus. The results of the present study demonstrate that different populations of neurons in the nucleus of the solitary tract contribute to ascending and descending pathways. This suggest a possible functional specialization within the nucleus of the solitary tract for those neurons whose output eventually reaches the forebrain compared to those neurons with local connections.

Differential projections from gustatory responsive regions of the parabrachial nucleus to the medulla and forebrain

The present study combined extracellular electrophysiology with anterograde and retrograde tracing techniques to determine efferent projections from taste responsive sites within the parabrachial nucleus (PBN). Taste activity was recorded from two distinct regions of the PBN, the waist region consisting of the ventrolateral (VL) and central medial (CM) subnuclei, and the external region, consisting of the external medial (EM) and external lateral (EL) subnuclei. Ascending and descending projections from these two regions differed. Small biotinylated dextran injections placed in taste responsive sites in the waist area produced a prominent descending projection to the medullary parvocellular reticular formation, a projection nearly non-existent from the external region. Differences in ascending projections were more subtle. Projections to the thalamus were bilateral in all cases, however, the waist region had a larger ipsilateral thalamic projection than the external region and the external region had a larger contralateral projection compared to the waist. Central nucleus of amygdala (CNA) projections from the waist area were primarily from posterior tongue responsive sites in VL and terminated in the central medial and lateral CNA subnuclei; external region projections were distributed to the capsular region of CNA. Both the external and waist region projected to substantia innominata (SI). Different efferent projections from the two gustatory responsive regions of the PBN may reflect functional specialization of PBN subnuclei. Descending projections from orally responsive sites in the waist area project to the lateral parvocellular reticular formation, a region implicated in brainstem circuitry underlying consummatory components of ingestive function. The external region, contains cells responsive to pain and oral aversive stimuli, but does not apparently contribute directly to local brainstem functions. Rather, forebrain pathways appear critical to the expression of external region functions.

Efferent projections from the anterior nucleus of the solitary tract of the hamster

The efferent projections from the anterior nucleus of the solitary tract (NST) of the golden hamster (Mesocricetus auratus) were determined using both anterograde and retrograde techniques. Injections of [3H]leucine were made into the anterior NST in regions responsive to gustatory stimulation of the anterior tongue. Ascending projections to the parabrachial nuclei (PBN) were evident as were projections within the NST and subjacent reticular formation. The cells of origin for both ascending and descending pathways were characterized by deposits of HRP into the PBN and caudal medulla. Cells projecting to the PBN were located in the dorsal and dorsolateral anterior NST in contrast to cells from the ventral region of the anterior NST which project within the medulla. Neurons in the reticular formation ventral to the anterior NST project to both regions. These local projections adjacent to oral motor nuclei provide an anatomical basis for the anterior nucleus of the solitary tract to influence oro-motor responses.

Neurotransmitter phenotypes of intermediate zone reticular formation projections to the motor trigeminal and hypoglossal nuclei in the rat

Numerous studies suggest an essential role for the intermediate (IRt) and parvocellular (PCRt) reticular formation (RF) in consummatory ingestive responses. Although the IRt and PCRt contain a large proportion of neurons with projections to the oromotor nuclei, these areas of the RF are heterogeneous with respect to neurotransmitter phenotypes. Glutamatergic, GABAergic, cholinergic, and nitrergic neurons are all found in the PCRt and IRt, but the projections of neurons with these phenotypes to the motor trigeminal (mV) and hypoglossal nucleus (mXII) has not been fully evaluated. In the present study, after small injections of Fluorogold (FG) into mV and mXII, sections were processed immunohistochemically to detect retrogradely labeled FG neurons in combination with the synthetic enzymes for nitric oxide (nitric oxide synthase) or acetylcholine (choline acetyltransferase) or in situ hybridization for the synthetic enzyme for GABA (GAD65/67) or the brainstem vesicular transporter for glutamate (VGLUT2). In three additional cases, FG injections were made into one motor nucleus and cholera toxin (subunit b) injected in the other to determine the presence of dual projection neurons. Premotor neurons to mXII (pre‐mXII) were highly concentrated in the IRt. In contrast, there were nearly equal proportions of premotor‐trigeminal neurons (pre‐mV) in the IRt and PCRt. A high proportion of pre‐oromotor neurons were positive for VGLUT2 (pre‐mXII: 68%; pre‐mV: 53%) but GABAergic projections were differentially distributed with a greater projection to mV (25%) compared to mXII (8%). Significant populations of cholinergic and nitrergic neurons overlapped pre‐oromotor neurons, but there was sparse double‐labeling (<10%). The IRt also contained a high proportion of neurons that projected to both mV and MXII. These different classes of premotor neurons in the IRt and PCRt provide a substrate for the rhythmic activation of lingual and masticatory muscles. J. Comp. Neurol. 487:28–47, 2005.

The contribution of gustatory nerve input to oral motor behavior and intake-based preference. II: Effects of combined chorda tympani and glossopharyngeal nerve section in the rat

Two-bottle intake tests and taste reactivity (TR) tests were used to reveal whether changes in ingestive behavior would follow bilateral section of either the chorda tympani (CT) or the glossopharyngeal (GP) nerve. Rats received two-bottle intake tests to compare 24-h ingestion of water to that of NaCl, MgCl2, quinine, or sucrose. Prior to each long-term intake test, rats received a 1 min, 1 ml intraoral infusion of the same chemical stimulus. Ingestive and aversive oral motor responses elicited by these 1 ml infusions were videotaped and subsequently analyzed. GP-section did not alter quinine or sucrose preference; overall, preference of MgCl2 and NaCl was also similar to controls. In contrast, TR tests in GP-sectioned rats revealed that most quinine, MgCl2 and NaCl stimuli elicited significantly fewer aversive oral motor responses. In addition, the latency of aversive responses to these 3 chemical stimuli was increased for these rats. Intake-based preference tests failed to show any difference between rats with CT nerve section and controls. In TR tests, however, CT-sectioned rats displayed significantly fewer ingestive oral motor responses to NaCl, MgCl2, and quinine than controls. Neither sucrose intake nor sucrose-elicited TR were altered by CT or GP nerve section. This report confirms the failure of long-term intake tests to uncover behavioral deficits following the section of gustatory nerves. In contrast, the use of a different behavioral test makes clear for the first time that gustatory nerve section has dramatic consequences on ingestive behavior. The examination of taste elicited oral motor behaviors reveals a coherent and nerve specific pattern of neurological deficit following peripheral nerve section.

Identification of lingual motor control circuits using two strains of pseudorabies virus.

First-order interneurons that project to hypoglossal motoneurons are distributed within reticular formation subdivisions in the pons and medulla in areas thought to control licking, swallowing, chewing, and respiration. Movement of the tongue in each of these functions is achieved by the coordinated action of both intrinsic and extrinsic lingual muscles. Interneuron populations that project to these different lingual motoneuronal pools appear to be largely overlapping in the reticular formation. Because of the functional coupling between intrinsic and extrinsic muscles during most tongue movements, one might predict that individual pre-hypoglossal interneurons project to multiple motoneuronal pools. To test this hypothesis, one strain of pseudorabies virus was injected into the styloglossus muscle (an extrinsic lingual muscle) and a second strain of pseudorabies virus was injected into the intrinsic lingual muscles of the anterior tongue in the same preparation. Rats were perfused with fixative 84-96 h later, and dual-labeling immunohistochemistry was performed to reveal populations of single- and double-labeled brainstem neurons. Motoneurons innervating the different lingual muscles were spatially segregated within the hypoglossal motor nucleus, and no double-labeled motoneurons were observed. In contrast, pre-hypoglossal neurons projecting to each lingual motoneuron pool were highly overlapping in the reticular formation, and many were double-labeled. These observations suggest that coactivation of lingual muscles can be achieved, at least in part, through divergent projections of first-order interneurons to anatomically and functionally distinct pools of lingual motoneurons in the hypoglossal nucleus.

Gustatory and tactile stimulation of the posterior tongue activate overlapping but distinctive regions within the nucleus of the solitary tract

Both the gustatory and somatosensory systems provide necessary sensory input for the initiation and control of oromotor behaviors. Behavioral studies indicate that somatosensory input from the posterior tongue (PT) is important in initiating swallowing, whereas PT taste input is particularly important in gustatory rejection reflexes. However, there have been few studies of the central representation of PT gustatory or tactile responses. In the present study, electrophysiological multi-unit recording techniques were used to map the location of PT-mediated taste and tactile responses in the nucleus of the solitary tract (NST) of the rat. A stimulation technique that allows taste stimuli to be introduced directly and specifically into the papillae trenches was used to optimally activate PT taste receptors located within the circumvallate (CV) and foliate (FOL) papillae. The results demonstrated that non-PT responsive sites dominated the rostral half of the rostral division of NST (rNST), while PT-responsive sites dominated the caudal half. Some PT-responsive sites extended into the caudal NST. Both gustatory and tactile stimuli were effective at 28% of PT-responsive locations (taste-tactile sites), whereas at the remaining locations, only tactile stimulation was effective (tactile-only sites). Although these two types of PT-responsive sites exhibited some anatomical overlap, their distributions were distinctive, with taste-tactile sites restricted medially and the laterally located tactile-only sites offset caudally. On the other hand, responses arising from stimulation of the CV and FOL exhibited no anatomical organization, i.e., responses to stimulation of both papillae were coexistensive. On average, of the four tastants used (0.01 M Na saccharin, 0.3 M NaCl, 0.01 M quinine hydrochloride, 0.03 M HCl), HCl was the most effective stimulus for both the CV and FOL. The present results delimit the regions of the NST that provide a substrate for the gustatory and somatosensory limbs of PT-mediated oromotor reflexes.

Fos-like immunoreactivity in the brain stem following oral quinine stimulation in decerebrate rats

The present study compared the distribution of Fos-like immunoreactivity (FLI) following intraoral stimulation with quinine monohydrochloride (QHCl) in awake intact rats to the pattern obtained in chronic supracollicular decerebrate (CD) rats. Because the behavioral rejection response to QHCl is evident in the CD rat, it was hypothesized that the pattern of FLI in the lower brain stem should be similar in both groups. Overall, the distribution of FLI in the brain stem was quite similar in both intact and CD groups, and QHCl stimulation increased FLI in the rostral (gustatory) nucleus of the solitary tract, the parabrachial nucleus (PBN), and the lateral reticular formation (RF) compared with an unstimulated control group. The CD group differed from the intact group, however, with a trend toward less FLI in the RF and a shift in the pattern of label away from the external subdivision of the PBN. CD rats also had increased FLI in the caudal nucleus of the solitary tract, with or without intraoral infusions. The distribution of QHCl-induced FLI in the brain stem of intact rats thus indicates both local sensorimotor processing as well as the influence of forebrain structures.

Photoperiod-mediated impairment of long-term potention and learning and memory in male white-footed mice.

Adult mammalian brains are capable of some structural plasticity. Although the basic cellular mechanisms underlying learning and memory are being revealed, extrinsic factors contributing to this plasticity remain unspecified. White-footed mice (Peromyscus leucopus) are particularly well suited to investigate brain plasticity because they show marked seasonal changes in structure and function of the hippocampus induced by a distinct environmental signal, viz., photoperiod (i.e. the number of hours of light/day). Compared to animals maintained in 16 h of light/day, exposure to 8 h of light/day for 10 weeks induces several phenotypic changes in P. leucopus, including reduction in brain mass and hippocampal volume. To investigate the functional consequences of reduced hippocampal size, we examined the effects of photoperiod on spatial learning and memory in the Barnes maze, and on long-term potentiation (LTP) in the hippocampus, a leading candidate for a synaptic mechanism underlying spatial learning and memory in rodents. Exposure to short days for 10 weeks decreased LTP in the Schaffer collateral-CA1 pathway of the hippocampus and impaired spatial learning and memory ability in the Barnes maze. Taken together, these results demonstrate a functional change in the hippocampus in male white-footed mice induced by day length.