Uninjured aged sympathetic neurons sprout in response to exogenous NGF in vivo.

The extent to which the loss of plasticity by aged neurons is due to changes in the neuronal environment or to a loss of growth potential of the neurons has not been determined. In previous studies we observed that young adult cerebrovascular axons undergo a sprouting response following a 2-week intracerebroventricular infusion of nerve growth factor (15 microg; NGF). The present study used electron microscopy to examine the innervation of the intradural segment of the internal carotid artery of the aged rat and to determine whether aged sympathetic perivascular axons would respond to in vivo infusion of NGF. Young adult and aged Fischer 344 female rats received a 2-week intracranial infusion of NGF (15 microg) or vehicle (VEH) and were perfused for electron microscopy. Although there was no change in the total number of perivascular axons associated in aged VEH when compared with young adult VEH, a significant reduction was observed in aged VEH when total axons and sympathetic axons were expressed per microm2 vascular wall, reflecting an age-related increase in blood vessel size. Following NGF infusion, aged sympathetic axons were significantly increased by 192% compared with aged VEH cases. These results suggest that there is a proportional reduction in sympathetic cerebrovascular neurons with aging but that they exhibit robust sprouting in response to an exogenous neurotrophin.

Plasticity of aged perivascular axons following exogenous NGF: analysis of catecholamines.

The present study investigated the atrophy of aged perivascular sympathetic axons and the response of these cerebrovascular neurons to the neurotrophin nerve growth factor (NGF). Using high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) to quantify catecholamines and immunohistochemical methods to quantify the density of TH immunoreactive fibers, we found a significant decrease in norepinephrine (NE) and TH in aged sympathetic axons. However, following in vivo administration of exogenous neurotrophin, aged neurons exhibited a robust response to NGF that was similar to the young adult, suggesting little decline in the capability of aged neurons to utilize exogenous neurotrophin. These results suggest that the age-related atrophy of aged sympathetic axons may result primarily from reduced availability of target-derived neurotrophin rather than from intrinsic alterations of neuronal function.

Intracerebral NGF infusion induces hyperinnervation of cerebral blood vessels.

The use of intracerebral NGF (nerve growth factor) infusions as a therapeutic tool to prevent the degeneration of cholinergic neurons in humans suffering from Alzheimer's disease has recently been suggested. In the present study, intracerebroventricular infusion of nerve growth factor into the adult rat brain was found to induce axonal sprouting of mature, uninjured axons associated with the intradural segment of the internal carotid artery. Following NGF infusion, a three-fold increase in the total number of axons associated with the vessel wall was observed when compared with vehicle-infused animals. This vascular hyperinnervation might also occur in humans. Before NGF infusion therapy is initiated, more research is necessary concerning the specificity, mechanisms, and functional significance of the sprouting response observed in this study.

Cholinergic innervation of canine thalamostriatal projection neurons: an ultrastructural study combining choline acetyltransferase immunocytochemistry and WGA-HRP retrograde labeling.

Choline acetyltransferase (ChAT) immunocytochemistry and lectin-conjugated horseradish peroxidase (WGA-HRP) histochemistry were combined at the electron microscopic level to examine the morphology of cholinergic terminals in the canine centrum medianum-parafascicular complex (CM-Pf) and to localize cholinergic terminals making synaptic contact with retrogradely labeled CM-Pf thalamostriatal projection neurons. Following WGA-HRP injections into the caudate nucleus, CM-Pf neurons were heavily labeled with WGA-HRP reaction product. Examination with the electron microscope revealed retrogradely labeled neurons characterized by a large nucleus with deep infoldings of the nuclear envelope. ChAT-positive terminals were observed arising from small-diameter nonmyelinated axonal profiles. These terminals varied in size from 0.5 to 1.4 micron in long diameter. The smaller terminals (0.5-0.7 micron) were seen most frequently and established symmetrical or slightly asymmetrical synaptic contacts with small dendritic profiles. The larger ChAT-positive terminals (1.0-1.4 micron) were less frequently observed, contained several mitochondria and small clusters of pleomorphic vesicles, and contacted large dendritic shafts and cell somata. Some of the postsynaptic targets of both smaller and larger ChAT-positive terminals were identified as belonging to retrogradely HRP-labeled thalamostriatal neurons. These observations indicate that at least some thalamostriatal neurons within the CM-Pf complex are innervated by cholinergic terminals which probably arise from ChAT-positive cell bodies located within the pontomesencephalic tegmentum, particularly within the nucleus tegmenti pedunculopontinus and the laterodorsal tegmental nucleus. These findings provide evidence for direct influence by cholinergic brainstem nuclei over activities of thalamostriatal neurons.

Plasticity of mature sensory cerebrovascular axons following intracranial infusion of nerve growth factor.

Mature perivascular sympathetic axons associated with the intradural segment of the internal carotid artery (ICA) of the adult rat respond by sprouting following a two week infusion of nerve growth factor (NGF) into the lateral ventricle of the brain. Because nonsympathetic axons such as those comprising the sensory and parasympathetic population have been shown to respond to NGF, the present study was carried out to determine whether mature sensory axons respond to in vivo NGF infusion and whether competitive interactions between the innervating populations might affect the responsiveness of these axons to NGF. Standard electron microscopic techniques as well as calcitonin-gene-related peptide (CGRP) immunohistochemistry at the light microscopic level were used to examine the effects of intracerebroventricular NGF infusion on mature perivascular fibers with and without prior sympathetic denervation (i.e., bilateral superior cervical ganglionectomy). Following NGF infusion, CGRP-immunoreactive fibers appeared thicker and more numerous in the longitudinal plane when compared with vehicle controls. However, at the ultrastructural level, a significant increase in the total number of axons was not observed, although there was an increase in the number of large granular vesicles, suggesting that the CGRP fibers responded to exogenous NGF with an increase in neurotransmitter content, but not by sprouting. Sympathetic denervation, on the other hand, resulted in a significant increase in the number of fibers passing in the circumferential plane. The most dramatic change in CGRP immunoreactivity was observed following combined sympathetic denervation and subsequent NGF infusion, where, in addition to the presence of thicker immunoreactive fibers, a significant increase in the perivascular density of immunoreactive fibers associated with the intradural blood vessels was observed. These findings suggest that exogenous NGF has different effects on mature sympathetic and nonsympathetic fibers that innervate intradural blood vessels. The former exhibit robust sprouting, whereas the latter do not sprout in response to NGF but show evidence for increased neuropeptide content. In addition, the heightened response by sensory axons following denervation and subsequent NGF infusion provides support for the idea that sensory and sympathetic axons normally compete for target space and/or target-derived neurotrophic factors.

Thalamostriatal projections from the ventral anterior nucleus in the dog.

Thalamostriatal projections from the ventral anterior nucleus (VA) were mapped by using autoradiographic and horseradish peroxidase techniques in the dog. Injections of tritiated leucine and proline into the lateral, central, and medial parts of VA resulted in anterograde label over the dorsolateral, midlateral, and dorsal parts of the head of the caudate nucleus, respectively. The dorsolateral and midlateral parts of the caudate contained the heaviest label. No silver grains were located over the medial or ventral parts of the caudate. Light to moderate label was located over the most dorsal part of the putamen. After injections of lectin-conjugated horseradish peroxidase (WGA-HRP) into the dorsolateral or intermediate areas of the head of the caudate, retrogradely labeled cells were present in the lateral and central parts of VA, respectively. In cases with dorsolateral caudate injections, labeled cells formed a narrow dorsoventrally oriented band located in the lateral part of VA whereas in the case with a larger injection into midcaudate, large numbers of labeled neurons were scattered throughout the central area of VA. Retrogradely labeled cells were also found in the rostral part of the ventral lateral nucleus (VL). Injections of WGA-HRP into the medial part of the caudate resulted in only a few labeled cells located in the dorsomedial part of VA. Combining these data with those from other studies mapping neostriatal afferents from the cerebral cortex in the dog, it is apparent that the midlateral part of the caudate receiving input from VA also receives afferents from cortical area 6. Furthermore, the dorsolateral part of the caudate that receives input from the lateral part of VA also receives afferents from cortical area 4. These results indicate that the dorsal and lateral parts of the canine caudate nucleus may constitute important links in the transmission and integration of information related to complex motor activities.

Nerve growth factor-induced sprouting of mature, uninjured sympathetic axons.

The infusion of nerve growth factor (NGF) into the lateral ventricle of the mature rat brain elicits a sprouting response from axons associated with the intradural segment of the internal carotid artery. Using electron microscopic techniques, we observed a three-fold increase in the total number of perivascular axons. This NGF-elicited response is characterized by a dramatic reduction in glial cell ensheathment similar to that observed during development and by the presence of profiles devoid of organelles that may represent newly formed sprouts. In spite of the increase in axon number, no significant changes in the percentage of small, medium, or large axons were observed. The three-fold increase in the total number of axons was accompanied by an increase in the number of axons/fascicle but no change in the number of fascicles. This, along with the observation that a majority of sprouted axons were associated with other axons, supports the idea that the sprouted axons tend to associate preferentially with other axons. Bilateral superior cervical ganglionectomies following cytochrome C infusion indicate that approximately 60% of the axons associated with the internal carotid artery arise from the superior cervical ganglion and that the majority of axons contacting the smooth muscle layer arise from this ganglion. Sympathectomy following NGF infusion resulted in a 79% reduction in the total number of perivascular axons, demonstrating overwhelmingly that the majority of sprouted axons are sympathetic fibers. These results demonstrate that infusion of NGF into the mature rat brain results in the preferential sprouting of sympathetic axons associated with the internal carotid artery. These findings are consistent with the hypothesis that NGF normally plays a role in the regulation of autonomic cerebrovascular innervation in the adult animal and that mature, uninjured sympathetic neurons remain responsive to NGF.

The effects of deafferentation and exogenous NGF on neurotrophins and neurotrophin receptor mRNA expression in the adult superior cervical ganglion.

Levels of nerve growth factor (NGF) and neurotrophin-3 (NT-3) protein and neurotrophin receptor mRNA in adult sympathetic neurons were investigated following surgical removal of preganglionic input and/or in vivo administration of NGF. Expression of trkC and p75, but not trkA, was significantly decreased following a 3-week deafferentation of the superior cervical ganglion (SCG). Protein levels of NGF and NT-3 in the SCG were unchanged by deafferentation. A 2-week intracerebroventricular infusion of NGF without deafferentation resulted in enhanced mRNA levels of trkA, trkC, and p75 as well as significantly increased NGF and NT-3 protein in the SCG. When NGF infusion followed deafferentation, both trkA and p75 showed significant increases while trkC levels were similar to control values. NGF protein was not increased in the SCG when deafferentation preceded exogenous NGF, yet NT-3 was elevated and levels were similar to cases receiving NGF infusion only. These results support a role for preganglionic input in trkC and p75 expression in adult sympathetic neurons. The increased levels of NT-3 protein and trkC gene expression observed following NGF infusion suggest that NGF influences NT-3 regulation in adult sympathetic neurons. In addition, the present findings provide evidence that, when preganglionic input is removed prior to the NGF infusion, NT-3 effectively competes with NGF for trkA binding. Taken together, we propose that NT-3 may play a role in the robust sprouting of sympathetic cerebrovascular axons previously observed following NGF administration, particularly when deafferentation precedes the NGF infusion period.

Combined immunocytochemistry and autoradiographic retrograde axonal tracing for identification of transmitters of projection neurons.

A double labeling method is described which combines immunocytochemistry for identification of the neurotransmitter serotonin with autoradiographic retrograde axonal tracing using wheat germ agglutinin (WGA), N-[acetyl-3H]. The permanence, sensitivity, and distinctness of the two labels provide a valuable means for analyzing transmitter-identified projection neurons in the central nervous system. Combined immunohistochemical/autoradiographic preparations, following injections of WGA, N-[acetyl-3H] in the caudate-putamen of mice, revealed large numbers of serotonergic and fewer non-serotonergic raphe-striatal projection neurons.

Unsuspected language impairment in psychiatrically disturbed children: prevalence and language and behavioral characteristics.

OBJECTIVE: This study examined the prevalence of unsuspected language impairments in 4-12-year-old psychiatric outpatients. METHOD: Children (N = 399) were routinely screened with standardized language tests, and parents and teachers completed behavioral checklists. RESULTS: Results indicated that of 288 children referred solely for a psychiatric disorder, 99 (34.4%) had a language impairment that had not been suspected previously. These children had more subtle language impairments than did the 111 children referred with previously identified language impairments. Both children with unsuspected and previously identified language impairments had symptoms associated with attention-deficit hyperactivity disorder. Children with unsuspected language impairments had the most serious externalizing behavioral problems. CONCLUSIONS: Attention needs to be paid to screening children for language impairments and to helping adults understand how language disabilities impact on communication and behavior.

Maternal exposure to 1,1,2-trichloroethylene affects myelin in the hippocampal formation of the developing rat.

The effect of 1,1,2-trichloroethylene (TCE), an industrial solvent, on myelin in the dorsal hippocampus of the developing rat was investigated. Rat pups were exposed to TCE via their dams' drinking water while in utero and until they were sacrificed at 21 days of age. Frozen coronal sections through the dorsal hippocampus were stained for the presence of myelin using a modification of the Heidenhain procedure developed for frozen sections. A significant decrease in myelinated fibers was found in the stratum lacunosum-moleculare, an area comprised of distal dendritic profiles of CA1 pyramidal neurons which receive input from the entorhinal cortex. These findings suggest that the reduction in myelin in the hippocampus may be responsible, in part, for behavioral effects observed following TCE exposure.

CONCEALED TRANSEPITHELIAL POTENTIALS AND CURRENT RECTIFICATION IN TSETSE FLY MALPIGHIAN TUBULES

1. Electrophysiological techniques have been applied to tsetse fly Malpighian tubules for the first time. 2. In either Cl- or SO42- Ringer, both non-perfused and perfused tubules displayed transtubular potentials (Vt) at or close to 0 mV. Exposure to cyclic AMP elicited a marked secretory response and, in SO42- Ringer, a sharp (lumen-positive) increase in Vt. In Cl- Ringer, despite more than double the secretory response, there was little or no change in Vt. 3. Replacing Cl- with SO42- Ringer, in the presence of cyclic AMP, promptly increased Vt. In perfused tubules, this occurred irrespective of the Cl- or SO42- composition of the perfusate. 4. In Cl- Ringer, the transepithelial resistance (Rtrans) was less than half that previously reported in Malpighian tubules of other species. Cyclic AMP reduced Rtrans still further, whether tubules were bathed in Cl- or SO42- Ringer. 5. Current­voltage (I/V) plots often displayed current rectification, both before and more frequently after exposure to cyclic AMP, thus permitting estimation of both the electromotive force of the Na+ transport mechanism (ENa) and of the shunt resistance (Rshunt). Both ENa and Rshunt were markedly lower in tubules bathed in Cl- than in SO42- Ringer. Cyclic AMP was without effect on ENa and Rshunt, in either Cl- or SO42- Ringer. 6. In terms of the equivalent electrical circuit, the secretory response to cyclic AMP was due solely to a fall in resistance of the active transport pathway (Rseries). The absence of an appreciable Vt, in Cl- Ringer, is consistent with an apical Cl- shunt.

Electrical transients in the cell-volume response to cyclic AMP of the tsetse fly Malpighian tubule

1. Using cyclic AMP to stimulate perfused tsetse fly Malpighian tubules bathed in SO42- Ringer frequently causes an immediate but transient peak in transtubular potential (Vt), before stabilisation of Vt at an increased value. 2. These transients were investigated by monitoring the associated changes in cable properties and current­voltage (I/V) relationships. Tubules were perfused and bathed in either Cl- Ringer or SO42- Ringer (containing 8 mmol l-1 Cl-). 3. Tubules bathed in Cl- Ringer showed a transient swelling of the cells on exposure to cyclic AMP. Cable analysis confirmed the visually observed narrowing of the tubular lumen and revealed transient increases in core resistance (Rc) and transtubular resistance (Rt). As the cells returned to their initial volume, the lumen became distended, and Rc and Rt fell below their initial levels. These changes were accompanied by an increase, and a subsequent decrease, in the slope of the I/V plot. 4. None of the above changes was apparent in SO42- Ringer, other than a fall in Rt and in the slope of the I/V plot. 5. The results suggest that, in Cl- Ringer, cyclic AMP induces swelling of the tubular cells by promoting increased basolateral solute (and water) entry and that the subsequent rapid return to normal cell volume, with a concomitant progressive increase in the rate of tubular secretion, reflects the operation of a specific cell-volume regulatory mechanism of transepithelial transport. 6. The cyclic-AMP-induced peak that occurs in Vt in SO42- Ringer appears to be primarily due to a transient overshoot in the fall in series resistance (i.e. an increase in basolateral Na+ conductance), accompanied by a proportionately lesser increase in shunt resistance.

Remodeling of adult sensory axons in the superior cervical ganglion in response to exogenous nerve growth factor.

In previous studies, we found that a 2-week in vivo intracerebroventricular infusion of nerve growth factor (NGF) elicited a sprouting response by sympathetic perivascular axons associated with the intradural segment of the internal carotid artery. We hypothesized that NGF infused into the ventricular system would be internalized by responsive sympathetic cerebrovascular axons, retrogradely transported to parent cell bodies in the superior cervical ganglion (SCG), and subsequently released into the local ganglionic environment. Because fibers exhibiting immunoreactivity for calcitonin gene related peptide (CGRP) have been localized in the SCG, we used immunohistochemical methods to investigate whether a response by CGRP-immunoreactive axons in the SCG occurred following the proposed transport to and release of exogenous NGF in the ganglion. In consecutive tissue sections of the SCG stained for either CGRP or NGF, we found CGRP pericellular 'baskets' surrounding identified NGF-immunoreactive cell bodies. Nerve growth factor infusion resulted in a significant increase both in the number of CGRP pericellular baskets and in NGF-immunoreactive cell bodies. A significant positive correlation (r=0.95, P<0.05) between the pericellular baskets and NGF-immunoreactive cell bodies was observed, suggesting that intracranial projection neurons in the SCG released infused NGF (or possibly a converted signal) into the local ganglionic environment to elicit remodeling of CGRP fibers to form pericellular baskets. These findings were confirmed in sections double labeled for NGF and CGRP immunoreactivity. This remodeling suggests that exogenous NGF may mediate retrograde transneuronal plasticity, allowing for future in vivo examinations of the mechanisms involved in neurotrophin transport and release.

Sympathetic ingrowth to the trigeminal ganglion following intracerebroventricular infusion of nerve growth factor.

The objective of the present study was to examine the remodeling of uninjured sympathetic axons in the adult rat trigeminal ganglion following a 2-week in vivo intracerebroventricular infusion of NGF. The accumulation of infused NGF in the trigeminal was assessed using ELISA and sympathetic fibers were localized immunohistochemically with an antibody to tyrosine hydroxylase (TH). In addition, high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD) allowed for biochemical measurements of the catecholamines norepinephrine (NE) and dopamine (DA). Increased NGF protein in the trigeminal ganglion was paralleled by a significant increase in sympathetic fibers and pericellular plexuses (i.e. baskets) in the cell body regions. Some ganglia showed elevated NE following NGF infusion, yet the 88% increase in mean NE did not reach significance. Following bilateral removal of the sympathetic superior cervical ganglia (SCG), a significant reduction was observed in overall NE levels and in TH-immunoreactive (-ir) fibers in the cell body regions and peripheral branches, suggesting the SCG as the origin of the sympathetic ingrowth. However, mean DA levels as well as TH-ir fibers within the trigeminal central branch were unaffected by NGF infusion or removal of the SCG and likely resulted from intrinsic dopaminergic cell bodies. In conclusion, our data provide evidence that the increased availability of NGF in the young adult rat trigeminal ganglion observed following in vivo NGF infusion enhanced sympathetic associations with the sensory neurons in the trigeminal, supporting a role for NGF in the regulation of sympathosensory interactions.

Evidence for reduced accumulation of exogenous neurotrophin by aged sympathetic neurons.

The present study investigated the potential for neurotrophin uptake by cerebrovascular axons and subsequent accumulation in the aged superior cervical ganglion (SCG) following a two week intracerebroventricular infusion of nerve growth factor (NGF). In the SCG from aged rats, NGF protein levels declined significantly compared with the SCG from young adult rats. Following NGF infusion, perivascular axons from both young adult and aged rats showed intense NGF immunostaining. In addition, significant increases in NGF protein were shown using enzyme-linked immunosorbent assay (ELISA) and in counts of NGF immunopositive cell bodies in the SCG when compared with age-matched controls. NGF accumulation in ganglia from aged rats, however, was significantly less when compared with ganglia from young adult rats. The results of the present study suggest that NGF protein is significantly reduced in aged ganglia with the neurons retaining some capacity to take up and transport exogenous neurotrophin. Even so, the potential for NGF accumulation is dramatically reduced in aged rats when compared with that of young adult rats. While previous results have shown robust NGF-induced neurotransmitter responses by sympathetic neurons from the aged animal, the present finding of reduced accumulation of NGF in aged sympathetic neurons suggests an age-related difference in the utilization or transport of NGF.

Evidence that nerve growth factor mediates the formation of sensory pericellular baskets in the rat trigeminal ganglion.

A role for nerve growth factor (NGF) in the remodeling of sensory neurons in the trigeminal ganglion was examined. Intracerebroventricular NGF infusion and/or bilateral removal of the sympathetic superior cervical ganglia, both of which are believed to increase the availability of NGF to primary sensory neurons, resulted in a significant increase in the frequency of calcitonin gene-related peptide immunoreactive pericellular baskets. The results of this study suggest that increased NGF is sufficient to enhance the formation of sensory baskets in this ganglion, and provide evidence that NGF may mediate the formation of sensory baskets in the sensory ganglia following injury.

Dose-dependent response of mature cerebrovascular axons in vivo following intracranial infusion of nerve growth factor.

The perivascular axons associated with the intradural segment of the internal carotid artery undergo a sprouting response following intracerebroventricular infusion of nerve growth factor (NGF). The objective of the present study was to determine whether a relationship exists between the number of sprouted axons and the amount of NGF infused into the ventricular system. Using regression analysis, we observed a significant log-log relationship between the dose of NGF and number of axons. No significant relationship was observed for the control (VEH) group. A significant increase in axonal number was observed following infusion of 3.0 micrograms NGF and higher when compared with VEH treatment of similar concentration. Results of this analysis suggest that a maximal response to NGF is approximated at doses of 15 micrograms or higher. These findings suggest a dose-dependent relationship between the response of mature sympathetic cerebrovascular axons in vivo and the dose of exogenous NGF.

Effects of mercuric chloride on the resting membrane potentials of blue crab (Callinectes sapidus) muscle fibers.

The effects of concentrations of mercuric chloride ranging from 3.68 to 368 microM (1--100 ppm) on the resting membrane potentials of muscle fibers in the extensor muscle of the carpopodite in walking legs of adults blue crabs were investigated in vitro. Glass micropipettes filled with saturated solutions of potassium chloride and conventional electronic equipment were used. Resting membrane potentials in uncontaminated artificial sea water averaged -78 mV +/- 4 mV (S.E.M.). Mercuric chloride added to the control bath at 3.68 or 9.2 microM did not affect the resting membrane potentials. At 18.4 microM threshold effects were obtained in 50% of the preparations. At concentrations ranging from 25.7 to 368 microM progressive deterioration of membrane polarization occurred as the mercury concentration was increased. This effect was irreversible despite multiple washes with normal sea water. We conclude that mercuric chloride has very powerful toxic effects at the peripheral motor effector elements in blue crabs. These results do not, of course, rule out more central effects on enzymatic systems or neuronal networks.

Thalamic afferents of area 4 and 6 in the dog: a multiple retrograde fluorescent dye study.

In the present study, we compared the distribution of thalamocortical afferents of cortical area 4 to that of cortical area 6 in the dog, using fluorescent tracers. Multiple injections of combinations of two dyes (diamidino yellow dihydrochloride, Evans blue, fast blue, granular blue) were made into either the anterior and posterior sigmoid gyri or into the medial and lateral regions of the anterior sigmoid gyrus in the anesthetized dog. We found that the thalamic afferents of areas 4 and 6 arise from topographically organized bands of cells that traverse several thalamic nuclei and extend throughout the rostrocaudal extent of the thalamus. The most medial band included area 6-projecting neurons in the anterior nuclei, the rhomboid nucleus, the ventral anterior nucleus (VA), ventromedial nucleus (VM) and mediodorsal nucleus (MD). Within this band, cells projecting to medial area 6 a alpha tended to be more numerous in the anterior nuclei, anterior parts of VA and VM and anterior and caudal parts of MD. Fewer cells in MD but more cells in caudal parts of VA and VM projected to lateral area 6 a beta. Lateral bands of cells in central through lateral parts of VA and VL projected topographically to lateral area 4 on the anterior sigmoid gyrus and lateral through medial parts of postcruciate area 4. The most lateral band of cells in VL continued ventrally into the zona incerta. Area 4 also received input from VM and the central lateral (CL) and centrum medianum (CM) nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)