Prolonged changes in dopaminergic terminal excitability and short changes in dopaminergic neuron discharge rate after short peripheral stimulation in monkey

Time-courses of responses to peripheral somatosensory stimulation were studied in the nigrostriatal dopamine (DA) system by comparing rates of neuronal discharges with changes in nerve terminal excitability, an indicator of DA release. The excitability of DA nerve terminals in the putamen was assessed as probability for evoking an antidromic response in substantia nigra DA cells with electrical stimulation in an anesthetized monkey. At about 30-60% decrease of excitability was seen during and about 15 min beyond pain pinch stimulation (PPS) in 12 of 17 tested DA neurons, while 4 neurons showed a 40% increase. Discharge rates were decreased in 7 and increased in 5 of the 17 DA neurons during, but not after PPS. It is concluded that the release of DA in the striatum may be controlled in two ways: rapid reactions would be mediated by changes in discharge rate, while slower, prolonged responses could be due to presynaptic interactions with other striatal afferents.     

Selective blockade of excitatory caudate responses to nigral stimulation by microiontophoretic application of dopamine antagonists

The dopamine (DA) antagonists haloperidol (Hal), chlorpromazine (CPZ) and fluphenazine (Flu) were applied by microiontophoresis from 8-barreled micropipettes while action potentials were recorded from single neurons in the feline caudate nucleus (CN) which fired in response to afferent stimulation. These DA antagonists selectively blocked the 15--25 msec latency action potential elicited by stimulation of the substantia nigra (SN) without affecting responses to cortical or thalamic stimulation. These results suggest that dopamine is the transmitter of the excitatory response of caudate neurons to stimulation of the SN. No evidence for an inhibitory input to the caudate liberating DA was found.     

Presynaptic L-type Ca(2)+ channels on excessive dopamine release from rat caudate putamen

We investigated by means of behavioral and neurochemical studies the role of the nerve terminal L-type voltage sensitive Ca(2)+ channel on dopamine (DA) release. Microinjection of Bay K 8644 (BAYK), an L-type Ca(2)+ channel stimulant, into the rat caudate putamen increased locomotor activity and rearing behavior in a dose-dependent manner, whereas injections into the amygdala had no effect. DA receptor antagonists significantly blocked BAYK-induced hyperactivity. Significant increases of extracellular DA levels were detected by microdialysis 20 min after BAYK administration into caudate putamen and then declined. This increase was influenced by tetrodotoxin, an axonal Na(+) channel blocker. Pretreatment with nimodipine and nicardipine, but not nifedipine, which are 1, 4-dihydropyridine L-type Ca(2)+ channel antagonists, administered into the caudate putamen significantly blocked BAYK-induced hyperactivity and DA efflux. These results indicate that the extraordinary DA release in the caudate putamen was mediated by extreme stimulation of the nicardipine and nimodipine-sensitive L-type Ca(2)+ channel present in the nerve terminal of striatal DA neurons.     

Microstimulation of the primate neostriatum. II. Somatotopic organization of striatal microexcitable zones and their relation to neuronal response properties

Sensorimotor response properties of neostriatal neurons were characterized in conjunction with assessments of the motor effects of intrastriatal microstimulation in unanesthetized rhesus monkeys. Neuronal activity and microexcitability were assessed at 250- to 500-micron intervals and, in some cases, at 25- to 100-micron intervals. The results are based on the functional characterization of 878 putamen and 224 caudate neurons and analysis of the effects of microstimulation at each of these recording sites. Recording/stimulation sites were located between stereotaxic planes A6 and A22 in 81 microelectrode tracks from three monkeys. A total of 443 (50.4%) putamen neurons showed discrete responses to the sensorimotor examination. Of neurons with sensorimotor responses, 232 (52.4%) showed increased rates of discharge in relation to both active and passive movements of specific body parts. An additional 193 (43.6%) cells increased their rates of discharge only during the monkey's active movements of specific body parts. The remaining 18 (4.0%) cells appeared to respond exclusively to passive somatosensory stimulation. The sensorimotor response areas of putamen neurons ranged in size from an entire limb to a single joint. Putamen neurons were somatotopically organized throughout the rostrocaudal extent of the nucleus. Neurons with sensorimotor response areas involving the leg were located in the dorsolateral putamen, those with orofacial representations were located ventromedially, and those with arm representations were located in an intermediate position. Microstimulation evoked discrete movements of individual body parts at 21.6% of the 878 putamen sites. Over 95% (181/190) of the effective sites were located within the central half of the rostrocaudal extent of the putamen, between stereotaxic planes A10 and A17. The pattern of somatotopic organization revealed by microstimulation was the same as that derived from sensorimotor response properties of putamen neurons. Moreover, a close correspondence was observed between the movements evoked from a given SMZ and the functional properties of local neurons. In contrast to the results obtained in the putamen, none of the 224 stimulation sites in the caudate nucleus was microexcitable, and only 17 (7.6%) of the caudate neurons had definable sensorimotor response properties. This is consistent with the view that the primate putamen, by virtue of its anatomic connections with the sensorimotor and premotor cortical fields, is more directly involved in motor functions, whereas the caudate nucleus, by virtue of its connections with cortical "association" areas, is involved in more complex behavioral functions.     

Parallel alterations in Met-enkephalin and substance P levels in medial globus pallidus in Parkinson''s disease patients

Met-enkephalin (Met-enk) and substance P (SP) were measured by a combined high-performance liquid chromatography/radioimmunoanalysis method in medial (GPM) and lateral globus pallidus (GPL) from controls and from Parkinson's disease (PD) patients. All patients showed a similar marked ( > 90%) reduction in dopamine (DA) levels in putamen compared with controls. However, based on DA levels in the caudate nucleus, two subgroups of PD patients were differentiated. In patients with > 80% decrease in caudate nucleus DA content, there was a three-fold increase in both Met-enk and SP levels in GPM. In contrast, in patients showing an 50% reduction in DA content in caudate, levels of both peptides were markedly reduced ( 80%). Met-enk and SP levels in GPL were unchanged in PD. These results suggest that neurons containing Met-enk and SP projecting to GPM adapt according to the extent of degeneration in the substantia nigra in PD.     

Neurons of the pretectal area convey spinal input to the motor thalamus of the cat

Summary The aim of this study was to corroborate lesioning work (Mackel and Noda 1989), suggesting the pretectal area of the rostral midbrain acts as a relay between the spinal cord and the ventrolateral (VL) nucleus of the thalamus. For this purpose, extracellular recordings were made from neurons in the pretectal area which were antidromically activated by stimulation in the rostral thalamus, particularly in VL. The neurons were tested for input from the dorsal columns of the spinal cord, the dorsal column nuclei, and the ventral quadrant of the spinal cord. Latencies of the antidromic responses ranged between 0.6 and 3.0 ms (median 1.0 ms): no differences in latencies were associated with either location of the neurons in the pretectal area or with the site of their thalamic projection. Orthodromic responses to stimulation of ascending pathways were seen in the majority of neurons throughout the pretectal area sampled. Latencies of orthodromic responses varied considerably, with ranges of 0.9–9 ms, 6–20 ms, and 2.5–20 ms upon stimulating the dorsal column nuclei, dorsal columns, and ventrolateral quadrant, respectively. The shortest-latency responses to stimulation of the dorsal column nuclei or of the ventral quadrant were likely to be monosynaptic. Temporal and spatial facilitation of the responses to ascending input were common. The data show that neurons of the pretectal area are capable of relaying somatosensory input ascending from the spinal cord to the rostral thalamus. It is suggested that the pretectofugal output to VL converges with cerebellar input in VL neurons and becomes incorporated in cerebello-cerebral interactions and, ultimately, the control of movement.     

Interactions between visceral and cutaneous nociception in the rat. II. Noxious visceral stimuli inhibit cutaneous nociceptive neurons and reflexes

1. Nocigenic inhibition is the inhibition of neural, behavioral, or reflex responses to a nociceptive test stimulus produced by another, conditioning, nociceptive stimulus. The present study examines whether a natural noxious visceral stimulus, colorectal distension, used as a conditioning stimulus would inhibit neuronal or reflex responses to noxious cutaneous stimuli. Segmental effects of colorectal distension have been previously characterized; hence conditioning effects of colorectal distension on stimuli applied at sites distant (heterosegmental effects) and adjacent (perisegmental effects) to those areas of the spinal cord that receive the greatest afferent input from the colon were examined. The conditioning effects of colorectal distension were compared with those of noxious pinch. 2. Heterosegmental effects of colorectal distension were studied in 129 neurons located in the area of the trigeminal nucleus caudalis and cervical spinal dorsal horn. Steady-state activity (spontaneous activity or activity evoked by sustained pressure) of 106 of 129 trigeminal-cervical dorsal horn neurons was inhibited by both noxious colorectal distension (100 mmHg, 20 s) and noxious pinch of the tail; all neurons inhibited by colorectal distension were also inhibited by noxious pinch. Inhibition was graded with the intensity of the distending stimulus. The class 2-class 3 classification system (neurons excited by nonnoxious and noxious or only by noxious cutaneous stimuli, respectively) was roughly predictive of susceptibility to nocigenic inhibition, because 74 of 75 class 2 neurons tested were inhibited by noxious colorectal distension or noxious pinch and only 32 of 54 class 3 neurons were similarly inhibited. Five neurons were excited by colorectal distension, all of which were class 3 neurons. 3. Perisegmental effects of colorectal distension were observed in 100 L3-L5 spinal dorsal horn neurons. The spontaneous activities and responses during noxious test heating of the glabrous skin of the hindpaw of these neurons were affected in the same way by noxious (conditioning) colorectal distension. All neurons inhibited by colorectal distension (51 class 2 and 8 class 3 neurons) were also inhibited by noxious pinch of the nose or forepaw. The magnitude of the nocigenic inhibition of responses during heating of the hindpaw was graded with the intensity and duration of the noxious conditioning colorectal distension, was a function of the number of preceding distensions given to the rat, and outlasted the distending stimulus. Conditioning colorectal distension also produced a parallel shift to the right in stimulus-response functions relating responses of neurons to the intensity of the noxious test stimulus (42-50 degrees C).(ABSTRACT TRUNCATED AT 400 WORDS)     

Ionotropic glutamate receptor-mediated responses in the rat primary somatosensory cortex evoked by noxious and innocuous cutaneous stimulation in vivo

To examine the involvement of different ionotropic glutamate receptors in the mediation of responses evoked by noxious cutaneous stimulation, single unit recordings were made from 31 neurons in the primary somatosensory (SI) cortex of rats anesthetized with urethane. To compare synaptic receptor pharmacology across somatosensory submodalities, 13 of the neurons were also tested with an innocuous, cutaneous air jet stimulus. Mechanical (HT) responses, evoked by a 5-s noxious pinch, decayed gradually upon termination of the stimulus and lasted on average for 15.1+/-1.9 s (+/-SEM; n=10). An increase in baseline activity was also observed during noxious stimulus trials of 5-min stimulus intervals. A correlation between increase in mechanical or thermal HT responses and baseline activity was found for some neurons. However, the normalized ratios of the mechanical or thermal HT response to baseline activity during iontophoretic application of (RS)-3-(2-carboxypiperazine-4-yl)-propyl-l-phosphonic acid (CPP), an N-methyl-D-aspartic acid (NMDA) receptor antagonist (0.6+/-0.1; n=11, or 6-nitro-7-sulfamoylbenz[f]quinoxaline-2,3-dione (NBQX), an (RS)-alpha-amino-3-hydroxy5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist (0.8+/-0.1; n=11), suggest that the reductions in baseline activity did not account for the reductions of the mechanical or thermal HT responses observed, which were reduced proportionally more than the baseline activity. A 10-ms air jet evoked a biphasic increase in action potentials above an average background activity of 7+/-2 spikes/s (n=13). The early phase of this low-threshold (LT) response was within two or three 10-ms bins and had an average firing rate of 74+/-11 spikes/s evoked in the first 10-ms bin (n=13). In eight neurons, the early LT response was followed by a lower frequency excitatory component lasting an average of 415+/-92 ms. Iontophoretic application of CPP reduced responses evoked by a noxious pinch (21+/-10% of control responses; n=19) and a noxious thermal stimulus (24+/-18%; n=5). The fast component of the LT responses was only reduced to 85+/-4% (n=12). A slower component of the LT responses, when present, was also reduced by CPP (15+/-19%; n=4). Iontophoretic application of NBQX reduced responses evoked by a noxious pinch (42+/-12%; n=19) and a noxious thermal stimulus (63+/-16%; n=8). The fast component of the LT responses was reduced to 43+/-6% (n=12) and the slower component to 32+/-20% (n=6). These data show that both NMDA and AMPA/kainate receptors are involved in the mediation of SI high-threshold responses. This same combination of glutamate receptors also mediates low-threshold synaptic responses.     

Projection from dorsal column nuclei to dorsal mesencephalon

This study investigated the projection from the dorsal column nuclei (DCN) to the dorsal mesencephalon. Single-unit extracellular recordings were obtained from the DCN of alpha-chloralose anesthetized cats. Neurons were identified by standard antidromic stimulation criteria as projecting to the dorsal mesencephalon (M neurons), the diencephalon (D neurons), or to both regions (MD neurons). Fifty-two neurons could be antidromically activated from the dorsal mesencephalon. Of these, 31 could also be antidromically activated by stimulation in the diencephalon. An additional 34 neurons were studied that could be antidromically activated only from the diencephalon. Stimulation sites within the dorsal mesencephalon effective in antidromically activating M and MD neurons were in the caudal ventrolateral superior colliculus, the intercollicular area, and external nucleus of the inferior colliculus. Effective diencephalic stimulation sites were in the ventroposterolateral nucleus, the zona incerta, and the magnocellular division of the medial geniculate. The antidromic latencies to stimulation in the dorsal mesencephalon of M and MD neurons spanned a similar but wide range of values in contrast to the latencies to stimulation in the diencephalon of D neurons which were all short. Conduction velocities along the mesencephalic and diencephalic collaterals of MD neurons were similar. Many of the neurons projecting to the mesencephalon had receptive fields located proximally on the body. Most of the neurons had rapidly adapting responses to low-intensity mechanical stimulation of the skin. The major difference between the mesencephalic M and MD projection neurons and diencephalic projection D neurons was the larger percentage of neurons having proximal receptive fields in the former group. These findings are the first electrophysiological demonstration of a direct somatosensory input to the dorsal mesencephalon arising in the DCN. This input is probably responsible for providing some of the somatosensory input to the deeper layers of the superior colliculus, the external nucleus of the inferior colliculus, and the intercollicular area, regions known to have neurons responding to somatosensory stimuli.     

Effects of chronic dorsal column lesions on pelvic viscerosomatic convergent medullary reticular formation neurons

Single medullary reticular formation (MRF) neurons receive multiple somatovisceral convergent inputs originating from many different spinal and cranial nerves, including the pelvic nerve (PN), dorsal nerve of the penis (DNP), and the abdominal branches of the vagus. In a previous study, the input to MRF from the male genitalia was shown to be eliminated with chronic 30-day dorsal hemisection at the T8 spinal level. In this study, the effect of a smaller chronic lesion [dorsal column lesion (DCx)] on MRF neuronal responses was examined. Responses to bilateral electrical stimulation of the DNP remained. MRF neuronal responses to non-noxious (touch/stroke) levels of penile stimulation, however, were eliminated; only responses to noxious pinch remained. No differences were found for the number of neurons responding to noxious distention of the colon between the DCx and control groups. Although no differences were found across these groups for the percent MRF responses to vagal stimulation, the mean response latency for the DCx group was twice the sham-DCx/intact control group. Taken together, these results indicate that the MRF receives at least some of its input from the male genitalia via pathways located within the dorsal columns at the mid-thoracic spinal level.     

Evidence that histochemically distinct zones of the primate substantia nigra pars compacta are related to patterned distributions of nigrostriatal projection neurons and striatonigral fibers

Summary A marked histochemical compartmentalization is visible in the substantia nigra of the squirrel monkey in sections stained for acetylcholinesterase (AChE). In nigral regions containing tyrosine hydroxylase-positive neurons, there are AChE-poor and AChE-rich zones, and many of the AChE-poor zones have the form of narrow fingers extending ventrally into an AChE-rich matrix (Jimenez-Castellanos and Graybiel 1987b). The study reported here was carried out to determine whether this histochemical heterogeneity of the primate's substantia nigra is related to the known differentiation within its pars compacta of subdivisions projecting respectively to the caudate nucleus and to the putamen. Retrograde and anterograde labeling in the substantia nigra was elicited by tracer injections placed in the caudate nucleus or putamen and was plotted in relation to patterns of AChE staining and tyrosine hydroxylase immunostaining. Much of the labeling observed was organized according to borders visible with AChE histochemistry: labeled nigral neurons (and afferent fibers) tended to be clustered precisely within the AChE-poor ventrally-extending fingers or to be situated outside these zones. However, projection neurons in these ventrally-extending fingers were not exclusively related either to the caudate nucleus or to the putamen. After injections in the caudate nucleus, labeled neurons were predominantly in the AChE-poor fingers in some cases, but predominantly in AChE-rich nigral zones outside them in other cases. Labeling in and out of the ventrally-extending fingers, and along the edges of the fingers, also occurred following different tracer injections in the putamen. These findings confirm the independent clustering of nigrostriatal neurons projecting respectively to the caudate nucleus and to the putamen. The plan of nigrostriatal connections additionally appears concordant with the histochemical compartmentalization of the substantia nigra that can be detected with acetylthiocholinesterase histochemistry.     

Striatal influences on paravermal cerebellar activity

Summary Units were recorded extracellularly in paravermal cortex (lobule VI) of the cerebellum of chloralose anesthetized cats. Electrical stimulation of the striatum evoked excitation followed by inhibition in these neurons. In addition, the somatosensory properties of these cells were also affected by the striatum. A conditioning-test paradigm (C-T) was used in which conditioning stimulation was applied to the striatum. Test responses were evoked in cerebellar neurons by facial stimulation. As a function of the C-T interval, striatal stimulation could either enhance or suppress the test facial responses. In another procedure, a moveable electrode was used to map the thresholds for affecting the cerebellum from different points in the striatum. The lowest mean threshold was in the putamen followed respectively by the internal capsule and caudate nucleus. Control experiments suggested that striatal effects on the cerebellum were due neither to extra-striatal current spread nor antidromic activation of corticostriatal fibers. These data were discussed with regard to models of striatal motor functioning that indicate a role in postural control and sensory gating.Supported by NIH grant NS 21418     

Vagal afferent inhibition of primate thoracic spinothalamic neurons

Spinothalamic (ST) neurons in the C8-T5 segments of the spinal cord were examined for responses to electrical stimulation of the left thoracic vagus nerve (LTV). Seventy-one ST neurons were studied in 39 anesthetized monkeys (Macaca fascicularis). Each neuron could be excited by manipulation of its somatic field and by electrical stimulation of cardiopulmonary sympathetic afferent fibers. LTV stimulation resulted in inhibition of the background activity of 43 (61%) ST neurons. Nine (13%) were excited, 3 (4%) were excited and then inhibited, while 16 (22%) did not respond. There was little difference among these groups in terms of the type of somatic or sympathetic afferent input although inhibited cells tended to be more prevalent in the more superficial laminae. The degree of inhibition resulting from LTV stimulation was related, in a linear fashion, to the magnitude of cell activity before stimulation. LTV inhibition of background activity was similar among wide dynamic range, high threshold, and high-threshold cells with inhibitory hair input. Any apparent differences in LTV inhibitory effects among these groups were accounted for by the differences in ongoing cell activity as predicted by linear regression analysis. LTV stimulation inhibited responses of 32 of 32 ST cells to somatic stimuli. In most cases the stimulus was a noxious pinch; however, LTV stimulation also inhibited responses to innocuous stimuli such as hair movement. Bilateral cervical vagotomy abolished the inhibitory effect of LTV stimulation on background activity (six cells) or responses to somatic stimuli (seven cells). Stimulation of the cardiac branch of the vagus inhibited activity of three cells to a similar degree as LTV stimulation, while stimulation of the vagus below the heart was ineffective in reducing activity of 10 cells. We conclude that LTV stimulation alters activity of ST neurons in the upper thoracic spinal cord. Vagal inhibition of ST cell activity was due to stimulation of cardiopulmonary vagal afferent fibers coursing to the brain stem, which appear to activate descending inhibitory spinal pathways. Vagal afferent activity may participate in processing of somatosensory information as well as information related to cardiac pain.     

Electrical stimulation of the anterior cingulate cortex reduces responses of rat dorsal horn neurons to mechanical stimuli

The anterior cingulate cortex (ACC) is involved in the affective and motivational aspect of pain perception. Behavioral studies show a decreased avoidance behavior to noxious stimuli without change in mechanical threshold after stimulation of the ACC. However, as part of the neural circuitry of behavioral reflexes, there is no evidence showing that ACC stimulation alters dorsal horn neuronal responses. We hypothesize that ACC stimulation has two phases: a short-term phase in which stimulation elicits antinociception and a long-term phase that follows stimulation to change the affective response to noxious input. To begin testing this hypothesis, the purpose of this study was to examine the response of spinal cord dorsal horn neurons during stimulation of the ACC. Fifty-eight wide dynamic range spinal cord dorsal horn neurons from adult Sprague-Dawley rats were recorded in response to graded mechanical stimuli (brush, pressure, and pinch) at their respective receptive fields, while simultaneous stepwise electrical stimulations (300 Hz, 0.1 ms, at 10, 20, and 30 V) were applied in the ACC. The responses to brush at control, 10, 20, and 30 V, and recovery were 14.2 +/- 1.4, 12.3 +/- 1.2, 10.9 +/- 1.2, 10.3 +/- 1.1, and 14.1 +/- 1.4 spikes/s, respectively. The responses to pressure at control, 10, 20, and 30 V, and recovery were 39.8 +/- 4.7, 25.6 +/- 3.0, 25.0 +/- 3.0, 21.6 +/- 2.4, and 34.2 +/- 3.7 spikes/s, respectively. The responses to pinch at control, 10, 20, and 30 V, and recovery were 40.7 +/- 3.8, 30.6 +/- 3.1, 27.8 +/- 2.8, 27.2 +/- 3.2, and 37.4 +/- 3.9 spikes/s, respectively. We conclude that electrical stimulation of the ACC induces significant inhibition of the responses of spinal cord dorsal horn neurons to noxious mechanical stimuli. The stimulation-induced inhibition begins to recover as soon as the stimulation is terminated. These results suggest differential short-term and long-term modulatory effects of the ACC stimulation on nociceptive circuits.     

Raphe magnus inhibition of feline T1-T4 spinoreticular tract cell responses to visceral and somatic inputs

Background activity of spinoreticular tract neurons in the T1-T4 segments was on average inhibited 80% by electrical stimulation of nucleus raphe magnus. Nucleus raphe magnus stimulation inhibited responses of spinoreticular tract neurons to somatic input produced by touching the skin and hair (innocuous stimulus) or pinching the skin and muscle (noxious stimulus). Inhibition of responses to noxious and innocuous somatic inputs was not significantly different. Inhibition produced during nucleus raphe magnus stimulation was less effective when the activity of spinoreticular tract cells increased. This relationship was consistent for both background activity and responses to somatic noxious or innocuous input. Nucleus raphe magnus stimulation inhibited responses of spinoreticular tract neurons to visceral input produced by electrical stimulation of cardiopulmonary sympathetic afferent fibers. Responses to C-fiber sympathetic afferent fibers were more effectively inhibited than were responses to A-delta sympathetic afferent fibers. In conclusion, stimulation of the nucleus raphe magnus inhibits T1-T4 spinoreticular tract neuronal responses to visceral and somatic inputs. Since spinoreticular neurons project to the medullary reticular formation, activation of the nucleus raphe magnus could modulate affective-motivational behavior and cardiovascular adjustments that often occur during angina pectoris.     

Topographical Fos induction within the ventral midbrain and projection sites following self-stimulation of the posterior mesencephalon

Rats will readily perform an operant response to self-administer electrical stimulation to the posterior mesencephalon (PM). Previous results show that axons that support self-stimulation travel between the PM and the ventral tegmental area (VTA) and that their activation increases firing of VTA neurons. The present work sought to extend these findings by describing the distribution of ventral midbrain neurons affected by PM self-stimulation. In Experiment 1, ventral midbrain Fos-immunoreactivity (IR) was assessed in three groups of rats implanted with a monopolar electrode; two groups were trained to self-administer stimulation, but only one was allowed to self-stimulate on the test day, whereas the third was never trained or tested. Self-stimulation induced prominent Fos-IR that was differentially distributed within the VTA and substantia nigra (SN). Control rats showed only sparse labeling. In Experiment 2, ventral midbrain Fos-IR was assessed with three additional groups trained to self-administer PM stimulation and tested as follows: Group-1 was allowed to self-stimulate, Group-2 received stimulation at parameters that failed to support self-stimulation (deemed non-rewarding) "yoked" to the rate of responding of Group-1, and Group-3 received no stimulation. PM self-stimulation induced Fos-IR throughout the rostral-caudal VTA and within the SN reticulata. Non-rewarding stimulation induced sparse Fos-IR, comparable to no stimulation. Fos-IR specific to PM self-stimulation was also observed within the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAS)-shell, but not within NAS-core, caudate putamen, medial prefrontal or orbital cortices. These findings are consistent with evidence that reward or positive reinforcement can be triggered by chemical and electrical stimulation over a large rostral-caudal extent of the VTA. They suggest that among ventral midbrain projection sites, the BNST and NAS-shell constitute important components of the circuitry implicated in reward. They provide additional support for the functional link between neurons that support PM and VTA self-stimulation, and offer topographical guidance to future attempts at their identification.     

Auditory response properties of neurons in the claustrum and putamen of the cat

Summary The auditory response properties of single neurons in claustrum and putamen were studied in response to simple dichotic stimuli (viz. noise- and tone-bursts) in chloralose-anaesthetized cats. Neurons in claustrum were commonly weakly driven with long latency, were broadly tuned and were excited by stimulation of either ear (EE). Putamen neurons, in contrast, were securely driven with short latency, showed irregular tuning with a preference for low frequencies and were either EE or excited only by the contralateral ear (EO). The differences between claustrum and putamen responses can be related to differences in connections with the auditory cortical fields and with auditory thalamus. Some neurons were also tested for visual responsiveness: auditory and visual cells were intermingled in both nuclei and only a small percentage of cells were bimodal. In contrast to the visual and somatosensory input to claustrum, which are derived from primary cortical fields, the auditory input to claustrum is apparently derived from non-primary cortical regions, suggesting a fundamentally different role for processing of auditory information in claustrum.     

The mode of projections of single locus coeruleus neurons to the cerebral cortex in rats

Axonal distributions of single locus coeruleus neurons within the cerebral cortex were examined with antidromic stimulation technique combined with cortical lesions (frontal lobotomy and lobectomy). In urethan-anesthetized rats, stimulating electrodes were implanted in 10 points extending over nearly the entire cerebral cortex, and antidromic responses of single locus coeruleus neurons to stimulation of these stimulus sites were analysed. Fifty percent of locus coeruleus neurons examined were activated antidromically from at least one cortical point in the cerebral cortex. The pattern and extent of axonal distributions of single locus coeruleus neurons in the cortex appeared to vary from cell to cell. From the results obtained in rats with the cortical lesions, it is concluded that in addition to locus coeruleus neurons with intracortical axons running from rostral to caudal, there are the neurons projecting to the occipital cortex without innervating the frontal cortex and those projecting simultaneously to the frontal and occipital cortex with two axonal branches. There was no topographic order between the recording sites within the locus coeruleus and the projection sites in the cortex.     

Monkey insular cortex neurons respond to baroreceptive and somatosensory convergent inputs

To investigate possible convergence of autonomic and somatosensory input in the insula of the non-human primate, extracellular single-unit recordings were obtained from 81 neurons (43 insular and 38 in surrounding cortex) during application of cutaneous nociceptive stimuli (pinch) and baroreceptor challenge in six anesthetized monkeys (Macaca fascicularis). All cells were also tested with light touch (brush) stimulation. Twenty-six units responded to blood pressure changes; 20 (80%) were identified within the insula (P < 0.001). The majority of these insular units (16/20) also responded to nociceptive pinch (convergent units). More units responsive to changes in blood pressure (unimodal and convergent) were found in the right (18/29, 62%) than in the left insular cortex (2/14, 14%)(P = 0.004). Twenty-nine insular neurons responded to nociceptive stimuli; 16 of these were convergent units and 13 showed unimodal responses to somatosensory stimuli alone. These cells had wide bilateral receptive fields including face, hand, foot and tail. Ten insular neurons were unresponsive to both sets of stimuli (non-responsive cells); significantly more of these cells (28/38) were identified in extrainsular locations (P < 0.01). We suggest that the primate insular cortex may be involved in the integration of cardiovascular function with somatosensory (principally nociceptive) input. This view supports the emerging role of the insular cortex as an important forebrain site of viscerosomatosensory regulation with clinical implications for cardiovascular regulation under conditions of stress and arousal.     

Clip-induced analgesia: noxious neck pinch suppresses spinal and mesencephalic neural responses to noxious peripheral stimulation

Pinch of the nape of the neck, of mice, with a serrated clip, produces immobility and lack of responsiveness to noxious stimulation. In this study we attempted to determine whether clip application produces true blockade of nociception, independent of its immobilizing effect, and examined the level of the neuroaxis at which such an effect takes place. To this end nociception was measured using indices not requiring a motor response. Neck pinch eliminated the elevation of heart rate induced by noxious pinch of the tail without affecting heart rate by itself providing evidence for its analgesic effect. Direct evidence that neck pinch suppresses the transmission of noxious information is also provided. Neck pinch inhibits neural activity evoked by noxious peripheral stimulation while exerting minimal effects on the effects of nonnoxious stimuli. Thus, sensory evoked activity in the periaqueductal gray area, elicited by noxious electrical stimulation, but not innocuous stimuli, is inhibited by neck pinch. Similarly, neck pinch inhibits the response of spinal cord neurons to noxious but not nonnoxious stimulation. It, therefore, appears that neck pinch produces true analgesia by activating supraspinal systems which in turn acts to inhibit the transmission of nociception both at spinal and supraspinal levels.