Leonard D. Aldes

Thalamic connectivity of rat somatic motor cortex

The purpose of this study was to investigate certain organizational features regarding the connectional relationships between the somatic motor cortex (SMI) and dorsal thalamus in the rat. This was accomplished by applying microiontophoretically horseradish peroxidase and tritiated amino acids into low threshold stimulation sites within hindlimb, forelimb and face representations of the SMI as defined by intracortical microstimulation. Injections into the SMI produced labeling in distinct sets of specific and non-specific thalamic nuclei. The former included the ventrolateral (VL), ventromedial (VM), posteromedial (Pom) and posterior (Po) nuclei, and the latter included the centrolateral (CL), paracentral (PC), centromedial (CeM) and parafascicular (PF) nuclei. The densest labeling, both retrograde and anterograde, was found in the VL, and to a slightly lesser extent, in the Pom nuclei. Labeling of specific nuclei was more extensive than in non-specific groups. Thalamic-SMI projections were reciprocal in nature with the exception of the reticular thalamic nucleus (R). The ventrobasal (VB) nucleus was labeled only after injections into the SMI representations of the hindlimb and forelimb. A topographic organization between the SMI and dorsal thalamic nuclei was indicated by the varied position of label following injections into different cortical representations. Injections into the hindlimb representation resulted in labeling in the rostrodorsolateral VL, ventrolateral VM, rostrodorsomedial Pom, dorsal Po, rostrodorsolateral R, dorsolateral PF, CL and PC. In contrast, injections into the face representation resulted in labeling in the caudoventromedial VL, dorsolateral VM, caudoventrolateral Pom, ventral Po, caudoventromedial R, ventrolateral PF, the PC, CeM and ventral CL. The position of thalamic labeling following injections into the forelimb representation was intermediate between that for hindlimb and face representations. In coronal section, distinct patterns of labeling were identified in all specific thalamic nuclei following injections into each topographic region of the SMI. In the VL, labeling appeared as an obliquely-oriented, longitudinal strip or band (more C-shaped following injections of the hindlimb representation); in the VM as a horizontal strip; in the Pom as an irregular V-shaped band; and in the Po as a circular-to-ovoid cluster. No distinct patterns of labeling were discerned in non-specific nuclei. Labeling in the anterior grouping of non-specific nuclei overlapped to a large extent, but this was not the case in either the specific thalamic nuclei or the PF nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Sources of noradrenergic afferents to the hypoglossal nucleus in the rat

The sources of noradrenergic (NA) innervation to the hypoglossal nucleus (nXII) in the rat were investigated with double-labeling histochemical/immunocytochemical and lesion/degeneration techniques. Following injection of wheat germ-agglutinin conjugated to horseradish peroxidase into nXII, brain stem sections were reacted with tetramethylbenzidine, stabilized, and incubated in antiserum to tyrosine hydroxylase (TH). Double-labeled neurons were observed in three pontine sites bilaterally, although mainly ipsilaterally, that included the nucleus subceruleus (nSC; 68.75%) and the A7 (21.09%) and A5 (10.15%) cell groups. Confirmation of the above results and identification of the course taken by descending NA-nXII projections was accomplished by lesioning the rostral pons, the nSC, or the medullary catecholamine bundle (MB), the suspected route by which NA afferents reach nXII. Quantitative estimates of the reduction of TH immunoreactivity on the lesioned compared to nonlesioned side of nXII were made densitometrically. In each case, TH immunostaining was significantly decreased (75%) in the ipsilateral caudoventromedial district of nXII, the predominant target area of NA input. The results from this study establish that multiple NA sources in the pons project to nXII in the rat, the majority of NA-nXII afferents are derived from the nSC, and descending NA-nXII projections course in the MB. These data are discussed relative to tongue control.

Serotonin-containing axon terminals in the hypoglossal nucleus of the rat. An immuno-electronmicroscopic study

The morphology and distribution of serotonin-containing axon terminals in the rat hypoglossal nucleus (XII) was investigated immunocytochemically at the electron microscopic level. Serotonin-positive profiles were found throughout all regions of XII and included unmyelinated axons, varicosities and axon terminals. Most labeled profiles (68.1%) were nonsynaptic unmyelinated axons and varicosities, while synaptic profiles, ending on dendrites and somata, were seen less frequently (28.7%). The majority of labeled axon terminals (76.9%) ended on small-to-medium-sized dendrites. Most axodendritic terminals contained small, round agranular vesicles (20-55 microns), several large (60-100 microns) dense core vesicles, and were associated with a pronounced asymmetric postsynaptic specialization. By contrast, labeled axosomatic terminals were seen less often than those ending on dendrites (23.0%). Axosomatic terminals typically contained small, round, agranular and large dense core vesicles and were associated with a symmetric or no postsynaptic specialization. These results provide the structural substrates for elucidating the functional role of serotonin in tongue control.

Differential distribution of biogenic amines in the hypoglossal nucleus of the rat

SummaryThe distribution of biogenic amines in the rat hypoglossal nucleus (nXII) was investigated with immunocytochemical methods using antibodies to tyrosine hydroxylase (TH) as a marker for catecholamines, and to 5-hydroxytryptamine (5-HT), the principal indoleamine, at the light microscopic level. TH and 5-HT immunoreactivity were found throughout all regions of nXII. Although the innervations overlapped, clearly differnt patterns of distribution were observed. TH immunoreactivity was localized primarily in the ventromedial quadrant of the caudal half of nXII and appeared largely as perisomatic-like profiles. In contrast, 5-HT immunoreactivity was greatest dorsally along the caudal half of nXII, although secondary foci of staining were evident ventrolaterally and, to a lesser extent, ventromedially. A perisomatic-like pattern of termination was observed for 5-HT in both dorsal and ventral regions of nXII. Since ventral and dorsal districts of nXII contain motoneurons that innervate protrusor and retrusor tongue muscles, respectively, we propose that the overlapping, yet differential distributions of catecholamines and indoleamines are important in controlling the relationships between functionally related groups of nXII motoneurons. These findings are discussed in relation to oro-lingual motor dysfunction.

Catecholamine innervation of the rat hypoglossal nucleus

The catecholamine innervation of the hypoglossal nucleus (XII) was investigated immunocytochemically by comparing the distribution patterns of tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the rat. Numerous TH- and DBH-positive profiles were found throughout XII, while only occasional PNMT immunoreactivity was observed. Significantly, the distribution patterns of TH and DBH immunoreactivity were coextensive with the most intense staining found ventromedially along the caudal half of XII. We conclude, therefore, that the catecholamine innervation of XII is largely noradrenergic, and that motoneurons innervating the genioglossi muscles, the principal protrusors of the tongue, are the primary targets of this input.

Interconnections between substantia Nigra reticulata and medullary reticular formation

Injections of wheat germ agglutinin-HRP into the medullary reticular formation (MRf) or the substantia nigra reticulata (SNr) revealed the presence of reciprocating fiber connections between the two areas. Large injections in the MRf demonstrated the existence of labeled neurons in the lateral portions of the SNr. Isolated injections into the parvocellular nuclei of the MRf resulted in the presence of terminal fields in the SNr particularly its lateral portions. Injections in the SNr resulted in the presence of labeled cells in the parvocellular nuclei. The significance of these findings is discussed in terms of oro-facial dyskinesias.

The enkephalinergic innervation of the genioglossus musculature in the rat: implications for the respiratory control of the tongue.

This study sought to determine if the enkephalinergic (ENK) innervation of the hypoglossal nucleus (nXII) in the rat was organized differentially for the control of the genioglossus musculature whose activity is essential in maintaining the patency of the upper airway. Immunocytochemical results revealed that the genioglossus motoneuron pool, comprising the ventrolateral subcompartment of the nXII, was consistently and heavily labeled throughout its rostrocaudal dimension. Labeling was characterized by dense focal clustering throughout the neuropil, and by the appearance of numerous perisomatic-like profiles. Similarly, the ventromedial subcompartment mainly rostrally, and the dorsal compartment caudally, whose motoneurons control the caudal intrinsic protrusor and rostral retrusor muscles, respectively, were also consistently labeled. While these results demonstrate that the genioglossus musculature is targeted by ENK inputs, they also suggest that other selected musculature of the tongue is controlled by ENK. It is argued that the innervation pattern identified in the present study is consistent with a functional role for ENK in the respiratory control of the tongue.

Pre- and postnatal development of the catecholamine innervation of the hypoglossal nucleus in the rat: an immunocytochemical study

The pre- and postnatal development of the catecholamine (CA) innervation to the hypoglossal nucleus (nXII) in the rat was investigated immunocytochemically with antisera to tyrosine hydroxylase (TH). Immunoreactive profiles positive for TH were first identified in nXII on gestational day (GD) 16. By GD 18, the adult-like distribution pattern was evident, characterized by the preferential targeting of the ventromedial region of nXII, but this pattern was not consistently found in all fetuses until GD 19. From GD 19 to postnatal day (PD) 180, the overall density of TH immunoreactivity, particularly in the ventromedial region, increased with further growth and maturation of nXII. These results establish the early prenatal CA innervation of nXII and support the hypothesis that CA are important in regulating motor tongue behavior in the newborn. Moreover, because the ventral compartment of nXII contains motoneurons that innervate protrusor muscles of the tongue, and tongue protrusor mechanisms play an essential role in suckling, deglutition, and respiratory (maintaining a patent upper airway) behaviors, it is further proposed that the CA innervation of nXII is critical to the survival of the newborn.

Ketamine-induced tongue protrusions in rats

1. The purpose of this study was to demonstrate that ketamine anesthesia (100 mg/kg) induces tongue protrusions (P) in addition to retrusions (R) and swallows (S) in adult rats. 2. These linguo-pharyngeal events occur alone or combined in various sequential patterns. 3. The SPR sequence is not the predominant pattern in all preparations suggesting profound disruption of physiological linkages by ketamine. 4. Haloperidol administration suppresses these events for 1-120 min depending on the dose (0.75-2.5 mg/kg). 5. Swallows are the least vulnerable to haloperidol. 6. This and previous findings provide further evidence that ketamine induced linguo-pharyngeal activity can serve as a model for acute or tardive dyskinesia better than stereotypies.

Effects of cholinergic and anticholinergic drugs on ketamine-induced linguopharyngeal motor activity

Benztropine mesylate (Cogentin) and physostigmine salicylate (Antilirium), were tested for changes in tongue protrusions, retrusions, and swallowing acts in rats anesthetized with a 100 mg/kg IM injection of ketamine hydrochloride. These ketamine-induced linguopharyngeal events were monitored by means of a force displacement transducer fed onto a polygraph. Benztropine (0.05–1 mg/kg) caused mild to moderate reductions in the rate of these events for a short period of time, up to about 30 min. With physostigmine (5–25 μg/kg), linguopharyngeal activity was markedly increased, up to 50-fold by the highest dose within 5 min and returned almost to the baseline within 60 min. With lower doses, more moderate responses were obtained. If methscopolamine (1.4, 3, 6 mg/kg IM) preceded physostigmine, the physostigmine enhancement was preserved.