Basal forebrain neurons projecting to the rat frontoparietal cortex: Electrophysiological and pharmacological properties

Neurons located in the ventromedial globus pallidus (nucleus basalis) and substantia innominata, that were antidromically driven by electrical stimulation of the frontoparietal cortex, were recorded in the urethane anesthetized rat. The basalocortical neurons (BCNs) were antidromically driven with latencies of 1.1-13.5 ms, giving conduction velocities of 0.6-6.8 m/s. Many BCNs had regular patterns of spontaneous discharge (mean spontaneous activity: 20 impulses/s). Most BCNs were not responsive to non-noxious peripheral somatic stimulation. BCNs were readily excited by the iontophoretic application of glutamate and strongly inhibited by GABA. Eighty-five percent of the BCNs could be excited by acetylcholine. They could also be excited by cholinergic agonists. Muscarinic agonists excited a higher proportion of BCNs than nicotinic agonists. Excitatory responses to acetylcholine, carbachol and muscarinic agonists were abolished by atropine.     

Ventral pallidal neuronal responses to dopamine receptor stimulation in the nucleus accumbens

The possible role of ventral pallidum (VP) in expressing dopaminergic actions in the nucleus accumbens was studied electrophysiologically using extracellular single unit recording and iontophoretic techniques in urethane-anaesthetized rats. Microinjections of dopamine (130 mM, 5-10 micrograms/0.2-0.4 microliters) into the nucleus accumbens resulted in a gradual, but prolonged, increase in the firing rate of VP neurones. Injections of the D1 agonist SKF38393 (34 mM, 2 micrograms/0.2 microliters), followed by the D2 agonist quinpirole (40 mM, 2 micrograms/0.2 microliters) into the accumbens, but not in the reverse order, resulted in a similar increase in the activity of VP neurones, mimicking the dopaminergic effect. Injections of either the D1 or the D2 agonist alone into the accumbens, however, produced no significant changes. Furthermore, iontophoretic application of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist, or naloxone, an opiate (including enkephalin) antagonist on the same VP neurone which responded to accumbens dopamine injection also increase its spontaneous firing rate. Thus, pre-activation of D1 receptors in the accumbens was essential for the subsequent physiological expression of D2 receptors in inducing an increase in the firing rate of VP neurones. Dopamine in the accumbens may suppress the tonic inhibitory GABAergic and enkephalinergic outputs to the VP, resulting in an increase in firing rate of VP neurones. Since previous behavioural studies have shown that dopaminergic stimulation in the accumbens increases locomotor activity, the increased firing rate of ventral pallidal neurones may be expressing the postsynaptic actions of dopamine receptor stimulations in the accumbens as initiation of locomotor activity.     

Excitatory effect of iontophoretically applied dopamine on identified neurons of the rat subthalamic nucleus

The effects of iontophoretic applications of dopamine were studied on neurons of the subthalamic nucleus (STN) identified by their histological location, their response to contralateral vibrissae stimulation and, for 33% of them, by their antidromic activation from the globus pallidus. A potent and consistent excitatory effect of dopamine was found for all the STN neurons tested. Depression of spontaneous activity or mixed responses were never recorded in the STN. The excitatory response was antagonized by iontophoretic application of flupenthixol.     

Evidence that an accumbens to subpallidal GABAergic projection contributes to locomotor activity

Neural projections from nucleus accumbens to subpallidal region, which contains a major GABAergic component, have been demonstrated with anatomical and electrophysiological techniques. The possible contribution of this GABA projection to the initiation of locomotor activity was investigated using neuropharmacological techniques. Injecting picrotoxin, a GABA antagonist, into the ventral globus pallidus increased locomotor activity measured in an open-field test, confirming findings. Locomotor activity was also increased when picrotoxin was injected into the lateral preoptic area, the sublenticular part of the substantia innominata and bed nucleus of the stria terminalis. In another series of experiments locomotor activity initiated by injecting dopamine into the nucleus accumbens was attenuated by pretreating the lateral preoptic area, the substantia innominata and ventral globus pallidus with GABA. These observations provide evidence that GABAergic projections from accumbens to subpallidal region contribute to locomotor activity and raise the possibility that they have a role in exploratory locomotion and in certain goal-directed behaviors.     

Auto- and cross-correlation analysis of subthalamic nucleus neuronal activity in neostriatal- and globus pallidal-lesioned rats.

Statistical analyses (autocorrelation and first-order interstimulus interval) were conducted on the spontaneous activity of over 420 subthalamic neurons recorded in 5 groups (control, large globus pallidus kainic acid lesion, partial globus pallidus kainic acid lesion, partial globus pallidus ibotenic acid lesion and neostriatal lesion) of anesthetized rats. Cross-correlation and peristimulus time histogram (to frontal motor cortex stimulation at 0.7 mA) analyses were conducted on pairs (n = 58) of subthalamic neurons recorded simultaneously on a single microelectrode. Lesion of the globus pallidus increased spontaneous firing rate as compared to controls and shifted the pattern of spontaneous activity from either a regular or irregular pattern to a markedly bursting pattern. Neostriatal lesion reduced firing rate and reduced the likelihood of highly regular firing. In control, neostriatal and partial lesioned animals, approximately 1 in 3 pairs of neurons showed correlated firing. The correlations were joint increased probabilities of firing over intervals of 200-400 ms, suggesting a shared excitatory input. No short-interval (less than 10 ms) correlations were seen. Large globus pallidus lesion increased the likelihood of correlated firing (12 of 16 pairs). In all groups of animals the peristimulus time histograms (PSTHs) to motor cortex stimulation were more similar than would be expected by chance and pairs of neurons showed the same increases in response following globus pallidus lesion. Thus adjacent neurons share common cortical inputs and responsiveness to those inputs. These changes indicate that the globus pallidus influences the spontaneous firing rate and pattern of subthalamic neurons as well as the degree of correlated firing of adjacent neurons.     

Effect of picrotoxin and nipecotic acid on inhibitory response of dopaminergic neurons in the ventral tegmental area to stimulation of the nucleus accumbens

Extracellular recordings were obtained from single neurons in the ventral tegmental area of rats anesthetized with urethane. It was found that the area appeared to contain two groups of neurons with distinctly different spike durations, firing rates and firing patterns. One group (group A) had properties similar to those of nigral dopaminergic neurons: slow random firing rates, unusually long spike durations and slow conduction velocities. The discharge rate of the majority of these neurons was reduced by iontophoretically applied dopamine. It was concluded that neurons of this group were probably A10 dopaminergic neurons. The other group (group B) had relatively faster and rhythmical firing rates, short spike durations and faster conduction velocities and were considered to be non-dopaminergic.Forty-nine units in the ventral tegmental area were antidromically activated by electrical stimulation of the nucleus accumbens. Units antidromically activated included neurons of group A and group B, suggesting that the nucleus accumbens received dual projections of dopaminergic and non-dopaminergic fibres from the ventral tegmental area.The discharge rate of 141 out of 142 neurons tested in the ventral tegmental area (group A: 66/66, group B: 75/76) was found to be reduced by GABA. The inhibition was blocked by the simultaneous application of picrotoxin. Picrotoxin alone activated 47.7% of 155 units tested. These results provide further evidence of a GABAergic input to dopaminergic and non-dopaminergic neurons projecting to the limbic forebrain structures.     

Alteration of neuronal responses in the subthalamic nucleus following globus pallidus and neostriatal lesions in rats

Kainic acid (2-4 days) or ibotenic acid (7-9 days) lesions of the globus pallidus or neostriatum altered the responsiveness of subthalamic nucleus neurons to electrical stimulation of the agranular frontal cortex. Three changes in responsiveness were seen following pallidal lesion: a) An increase in the proportion of responding cells as compared to controls (approximately 90% vs. 60%); b) an increase in the total duration of the evoked response (62.5 ms vs. 28.6 ms); 3) an increase in magnitude of response (9.76 spikes per stimulus vs. 3.24). Both an increase in firing rate (17.94 spikes/s vs. 8.23) and a change to a bursty spontaneous firing pattern were seen. Lesion of the neostriatum had fewer but opposite effects including decreased firing rate (7.21 spikes/s) and decreased total response duration (18.9 ms). These results suggest that the normal tonic inhibition of the subthalamic nucleus by the globus pallidus may play an important role in controlling subthalamic neuronal spontaneous activity and responsiveness. The neostriatum may influence the subthalamic nucleus via the globus pallidus. Globus pallidus lesions may have important consequences on the specificity of cortical control of the subthalamic nucleus and may alter subthalamic influence on basal ganglia output.     

Antidromic identification of dopaminergic and other output neurons of the rat substantia nigra

In the present study dopamine (DA)-containing and other output neurons of the substantia nigra (SN) wer identified by antidromic stimulation from postulated target nuclei, the caudate-putamen, the thalamus, the cortex and the pontine reticular formation. To guide electrode placements, the topography of the nigrostriatal projection system was determined by retrograde tracing methods. Spontaneously active cells present in the SN were then classified in two groups according to the shape of their action potentials and their firing rate. Type I cells were located mainly in the pars compacta and could be antidromically-activated (AD-activated) from various locations along the course of the nigrostriatal pathway (caudate-putamen, globus pallidus, MFB) but not from other brain areas (ventromedial thalamus, motor cortex, pontine reticular formation). These neurons had a slow bursting pattern of firing, a very slow conduction velocity (0.58 m/sec), and a wide action potential. Their firing rate was dramatically reduced following the intravenous administration of apomorphine (ID 50: 9.3 microgram/kg), or the iontophoretic application of DA and GABA. Type II cells were located predominantly in the pars reticulata; most of them could be AD-activated from the ventromedial thalamus and the MFB but not from the motor cortex. A few of these cells could be AD-activated from the pontine reticular formation and the thalamus. A minority of type II cells, located in or near the pars compacta could be AD-activated from the caudate-putamen. In addition, their conduction velocuty was much higher (2.8 m/sec) and their firing rate far in excess of that exhibited by type I neurons. These neurons were inhibited by the iontophoretic application of GABA but not of DA. The microinjection of 6-hydroxydopamine (a neurotoxin relatively specific against catecholamine-containing neurons) in the vicinity of the MFB blocked selectively the propagation of antidromic spikes in type I but not type II cells. It is concluded that type I cells are the DA neurons of the nigrostriatal pathway. Type II cells are mainly oupput neurons that project to the ventromedial thalamus, the pons and the forebrain. This telencephalic projection most likely constitutes a second, non-DA, fast-conducting nigrostriatal pathway.     

Periadolescent changes of D(2) -AMPA interactions in the rat nucleus accumbens

Many aspects of dopamine (DA) systems mature during adolescence. In the nucleus accumbens, the modulation of prefrontal cortical synaptic responses by DA becomes refined during adolescence with the recruitment of a gamma-amino butyric acid (GABA) component. As this GABA component is depolarizing, it remains to be determined whether this change affects action potential firing in nucleus accumbens neurons. Here we tested whether a D(2) agonist affects AMPA-evoked cell firing in slices containing the nucleus accumbens from juvenile (postnatal day, PD 28-34) and adult (PD > 60) rats. 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid (AMPA) (0.1-0.4 μM) depolarized nucleus accumbens neurons and increased their firing in a dose-dependent manner. The D(2) agonist quinpirole (2 μM) had different effects in juvenile vs. adult slices. In the juvenile accumbens, quinpirole enhanced AMPA (0.2 μM) effects on evoked firing in a subset of neurons while it had no effect on the rest. In the adult accumbens, the D(2) agonist instead attenuated the effect of AMPA on evoked firing, an interaction that was blocked by the GABA-A antagonist picrotoxin (50 μM). Thus, D(2) receptors modulate AMPA responses in the nucleus accumbens differently in juvenile than adult rats, and the adult effect requires local GABA transmission. The incorporation of a GABA component in the modulation of information processing in the nucleus accumbens by DA during adolescence may allow for a better contrast in cortically activated ensembles.     

Motor cortical control of internal pallidal activity through glutamatergic and GABAergic inputs in awake monkeys

The internal segment of the globus pallidus (GPi) receives motor-related cortical signals mainly through the striatum, the external segment of the globus pallidus (GPe) and the subthalamic nucleus (STN). The GPi sends its outputs outside the basal ganglia and plays a key role in motor control. Extracellular unit recordings were performed in awake monkeys to explore how glutamatergic STN inputs and GABAergic striatal and GPe inputs control spontaneous activity and how these inputs contribute to motor cortex stimulation-induced responses of GPi neurons. The typical responses of GPi neurons to cortical stimulation consisted of an early excitation, an inhibition and a late excitation. Local applications of the NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid and/or the AMPA/kainate receptor antagonist 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulphonamide in the vicinity of recorded GPi neurons reduced the firing rate, and abolished or attenuated both early and late excitations following cortical stimulation. Local application of the GABA_A receptor antagonist gabazine increased the firing rate, induced oscillatory firings and diminished the cortically induced inhibition. Muscimol or gabazine injection into the STN or GPe also altered the firing rate, and attenuated the late excitation of GPi neurons. The gabazine injection into the STN occasionally induced dyskinesia with significantly decreased GPi activity. These data suggest that the early and late excitations are glutamatergic and induced by the cortico-STN-GPi and cortico-striato-GPe-STN-GPi pathways, respectively. The inhibition is GABAergic and induced by the cortico-striato-GPi pathway. In addition, these inputs are the main factors governing the spontaneous activity of GPi neurons.     

High frequency stimulation of the STN influences the activity of dopamine neurons in the rat

The effect of high frequency stimulation (HFS) of the subthalamic nucleus (STN) on the spontaneous activity of substantia nigra pars compacta (SNc) dopaminergic neurons was investigated in normal rats and in rats with globus pallidus (GP) lesions. In normal rats, the spontaneous activity of SNc neurons did not significantly differ from that of rats with GP lesions (4.2+/-2.2 versus 4.4+/-2.6 spikes/s). STN-HFS induced an increase of firing rate in the majority of tested cells in normal (76%) and GP-lesioned rats (73%) with an after-effect of 34.4+/-3.4 and 33.2+/-3.1 s, respectively. These results demonstrate that STN-HFS influences the activity of the SNc dopaminergic neurons by increasing their firing rate and that this increase of activity is independent of the globus pallidus.     

Inhibitory short‐term plasticity modulates neuronal activity in the rat entopeduncular nucleus in vitro

The entopeduncular nucleus (EP) is one of the basal ganglia output nuclei integrating synaptic information from several pathways within the basal ganglia. The firing of EP neurons is modulated by two streams of inhibitory synaptic transmission, the direct pathway from the striatum and the indirect pathway from the globus pallidus. These two inhibitory pathways continuously modulate the firing of EP neurons. However, the link between these synaptic inputs to neuronal firing in the EP is unclear. To investigate this input–output transformation we performed whole‐cell and perforated‐patch recordings from single neurons in the entopeduncular nucleus in rat brain slices during repetitive stimulation of the striatum and the globus pallidus at frequencies within the in vivo activity range of these neurons. These recordings, supplemented by compartmental modelling, showed that GABAergic synapses from the striatum, converging on EP dendrites, display short‐term facilitation and that somatic or proximal GABAergic synapses from the globus pallidus show short‐term depression. Activation of striatal synapses during low presynaptic activity decreased postsynaptic firing rate by continuously increasing the inter‐spike interval. Conversely, activation of pallidal synapses significantly affected postsynaptic firing during high presynaptic activity. Our data thus suggest that low‐frequency striatal output may be encoded as progressive phase shifts in downstream nuclei of the basal ganglia while high‐frequency pallidal output may continuously modulate EP firing.     

The functional role of the nucleus accumbens in the control of the substantia nigra: Electrophysiological investigations in intact and striatum-globus pallidus lesioned rats

The effects of electrical stimulation of the nucleus accumbens on the activity of identified substantia nigra neurons were studied in intact and lesioned rats. The latter had both the caudate-putamen complex and globus pallidus destroyed by electrolytic lesions. In intact rats a total of 42 of 107 neurons (39.2%) responded to stimulation of the nucleus accumbens. Of the 107 neurons 32 (29.8%) were inhibited and 10 (9.4%) were excited. Pure short inhibitions, long latency inhibitions and excitations followed by inhibition were found in both parts of the substantia nigra. Pure long lasting inhibitions were determined on pars compacta cells only. In lesioned animals, in which the coactivation of striatal and/or cortical fibers traversing the accumbens region was avoided, the percentage of responsive neurons decreased to 20% (23/115). The predominant responses recorded in this situation were pure inhibitions of pars compacta cells (14/46) and long latency inhibitions of pars reticulata neurons (7/69). No pure excitation or excitation-inhibition sequence was recorded. In the two sets of experiments 5 cells were activated antidromically from the nucleus accumbens. The results provide electrophysiological evidence for an inhibitory pathway from the nucleus accumbens to the substantia nigra. The low percentage of responsive neurons, the lack of excitatory responses, the paucity of reciprocal connections and the different inhibitory effects on the two populations of nigral neurons demonstrate that the functional role of the nucleus accumbens in controlling the substantia nigra differs from that exerted by the striatum.     

Ventral pallidum projections to mediodorsal nucleus of the thalamus: an anatomical and electrophysiological investigation in the rat

Horseradish peroxidase (HRP) and single unit recording experiments were done in rats to investigate neural connections from the ventral pallidal region to the mediodorsal nucleus of the thalamus (MD). In the first series, following the diffusion or iontophoretic injection of HRP into the MD, retrogradely labeled neurons were observed throughout the rostrocaudal extent of the ipsilateral ventral pallidum. Most of the labeled neurons were found in an area between the nucleus of the diagonal band and the ventral aspect of the substantia innominata subcommissuralis. Additional labeled neurons were found in the ventral aspect of the globus pallidus and substantia innominata sublenticularis. In the second series, the region shown to contain labeled neurons was explored for single units antidromically activated by single pulse stimulation of the MD in urethane anesthetized rats. One hundred and fifty-nine single units in the subpallidal area were antidromically activated with latencies corresponding to conduction velocities of 0.2-3.9 m/s. A greater percentage of units in the subcommissural region (50.3%) were activated antidromically as compared to the sublenticular region (27.4%). In the third series, the MD was explored for single units which responded orthodromically to stimulation of the ventral pallidum. Fifty-eight percent (40/69) of MD units responded to stimulation of the subcommissural substantia innominata, whereas 90% (72/80) MD units responded to stimulation of the sublenticular substantia innominata. The most frequent type of orthodromic response observed in MD neurons was inhibition with short onset latencies (less than 10 ms). These data provide anatomical and electrophysiological evidence for the existence of direct pathways from the ventral pallidum to the MD and suggest that this projection is part of a corticosubcortical loop through which the frontal cortex with the ventral striatum and pallidum may contribute to motor function.     

Modulation of firing activity by endogenous GABAA receptors in the globus pallidus of MPTP-treated parkinsonian mice

The globus pallidus in rodents, equivalent to the external segment of the globus pallidus in primates, plays an important role in movement regulation. Previous studies have shown abundant γ-aminobutyric acid (GABA)ergic innervation and GABA_A receptors in the globus pallidus. In this study, we investigated the effects of endogenous GABA_A receptors on the spontaneous firing activity of pallidal neurons in both normal and MPTP-treated mice using multi-barrel electrodes extracellular recordings in vivo. We found that in normal mice, pressure ejection of 0.1 mmol/L gabazine, a specific GABA_A receptor antagonist, increased the spontaneous firing rate of globus pallidus neurons by 27.6 ± 5.6%. Furthermore, in MPTP mice (14 days after MPTP treatment), 0.1 mmol/L gabazine increased the firing rates by 51.0 ± 7.9%, significantly greater than in normal mice. These results suggest that endogenous GABA_A receptors modulate the activity of globus pallidus neurons. The present findings may provide a rationale for investigations into the potential role of GABA_A receptors in Parkinson’s disease.     

GABAergic projection from the ventral pallidum and globus pallidus to the subthalamic nucleus

There exists a topographically organized projection from the globus pallidus and ventral pallidum to the subthalamic nucleus and adjacent lateral hypothalamus. The participation of GABA as a neurotransmitter in this projection was evaluated by retrograde labeling of cells in the pallidal area from an iontophoretic deposit of Fluoro-Gold in the subthalamus combined with in situ hybridization for mRNA of the GABA synthetic enzyme, glutamate decarboxylase (GAD). A rostrocaudal gradient in the contribution of GABA to the projection was demonstrated with a relatively small percentage of retrogradely labeled cells in the rostra1 ventral pallidum containing GAD mRNA (7%) compared to the caudal globus pallidus which had over 70% of the Fluoro-Gold containing cells double-labeled for GAD mRNA. Overall the ventral pallidum contribution to the subthalamic nucleus was less GABAergic than the portion arising from the globus pallidus (35% vs. 61%, respectively). © 1995 Wiley-Liss, Inc.     

Effect of morphine applied by intrapallidal microdialysis on the release of dopamine in the nucleus accumbens

The effect of morphine, administered intrapallidally, on extracellular concentrations of DA, DOPAC, and HVA in the nucleus accumbens and striatum was studied in the behaving rat using the in vivo microdialysis technique. Unilateral application of morphine hydrochloride was perfomed through microdialysis probes into the rat ventral pallidum (10 μ1 of 0 2.6 4.0, 13.0, and 26.0 mM) or globus pallidus (10 μ1 of 0 and 26.0 mM). The levels of DA, DOPAC, and HVA were measured using the HPLC with EC detection in dialysates collected from the nucleus accumbens, anteromedial, and anterolateral striatum. Samples were taken every 45 min over 3 h before and over 5 h after morphine or vehicle administration. Administration of morphine into the ventral pallidum resulted in increased DOPAC and HVA concentrations in the nucleus accumbens. Pretreatment with naloxone (1 mg/kg, SC) abolished this effect of morphine. Administration of morphine into the globus pallidus resulted in increased DA, DOPAC, and HVA concentrations in the nucleus accumbens and DA in the anteromedial striatum. The levels of DA and metabolites in anterolateral striatum remained rather unchanged following morphine administered into the ventral pallidum or the globus pallidus. The changes in DA neurotransmission into the nucleus accumbens induced by morphine application into the ventral pallidum and globus pallidus are reminiscent of a phasic and tonic release of DA respectively. The results show that intrapallidal morphine increases DA neurotransmission in nucleus accumbens and suggest that the effect of morphine is mediated by ventral pallidum/mesolimbic and globus pallidus/thalamocortical pathways, depending on the site of injection.     

Neurotensin in projection neurons of the striatum and nucleus accumbens, with reference to coexistence with enkephalin and GABA: an immunohistochemical study in the cat

Neurotensin-like immunoreactivity (NT-LI) was demonstrated in projection neurons of the striatum and nucleus accumbens in the cat by combining immunohistochemistry and the fluorescent retrograde neuronal labeling method. In colchicine-treated cats, many neurons with NT-LI were found in the caudate nucleus, nucleus accumbens, and putamen. Most of these neurons were medium-sized neurons with spiny dendrites. NT-LI of neuronal elements in the caudate nucleus and nucleus accumbens formed dense aggregates with irregular figures, which appeared to correspond to the striosomes of Graybiel et al. (Proc. Natl. Acad. Sci. USA 75:5723-5726, '78; Exp. Brain Res. 34:189-195, '79; Neuroscience 6:377-397, '81). Fibers with NT-LI were distributed massively to the globus pallidus and ventral midbrain regions, but not to the entopeduncular nucleus. In the ventral midbrain regions, many fine varicose fibers with NT-LI were distributed to the pars compacta and pars lateralis of the substantia nigra, ventral tegmental area, and retrorubral area. In the pars reticulata of the substantia nigra, however, fibers with NT-LI were rather sparse. Examination of consecutive sections immunostained for NT, enkephalin (Enk), GABA, and substance P (SP) revealed that 50% of neurons with NT-LI in the caudate nucleus and nucleus accumbens exhibited Enk-LI, 15% showed GABA-LI, and 5% manifested both Enk-LI and GABA-LI; no NT-positive neurons in the striatum and nucleus accumbens showed SP-LI. No morphological differences were found between NT-positive neurons with Enk-LI and/or GABA-LI and those without Enk-LI and GABA-LI. Most neurons with NT-LI in the striatum and nucleus accumbens were retrogradely labeled with True Blue injected into the globus pallidus, pars compacta and pars lateralis of the substantia nigra, and ventral tegmental area. After hemitransection severing neuronal connections between the ventral midbrain regions and the forebrain structures, fibers with NT-LI and those with Enk-LI in the ventral midbrain regions were markedly reduced in number.(ABSTRACT TRUNCATED AT 400 WORDS)     

The spontaneous firing patterns of forebrain neurons. IV. Effects of bilateral and unilateral frontal cortical ablations on firing of caudate, globus pallidus and thalamic neurons

To assess the effects of partial deafferentation of the neostriatum on spontaneous neuronal activity in the basal ganglia and related thalamic nuclei, ablations of frontal cortex were carried out in adult cats. Postoperative measures of interspike intervals of single neurons in the caudate nucleus, globus pallidus and ventral anterior-ventral lateral complex of the thalamus revealed a slowing of neuronal firing in these structures as compared with non-lesioned controls. The fact that deafferentation by cortical damage produces changes in neuronal firing in target neurons of the striatum (globus pallidus) and in thalamic neurons at least two synapses removed from the striatum is noteworthy. The possible extent to which these results might have been influenced by reduction of cortical inputs to or denervation of the thalamus is discussed.     

Dopaminergic mechanisms in subthalamic nucleus of rat: analysis using horseradish peroxidase and microiontophoresis

Afferent connections to the subthalamic nucleus (STN) were studied by microiontophoretically injecting horseradish peroxidase (HRP) into the STN and studying its retrograde transport. Remotely labelled neurons were frequently observed in both the globus pallidus and the pars compacta region of substantia nigra. In addition, individually labelled neurons were occasionally found in other brain regions. The sensitivity of neurons in the STN to dopamine (DA) was studied by applying DA to neurons in the STN by microiontophoresis. Three patterns of response to DA were observed. The most frequent response, observed in 46% of the STN neurons studied, was a decrease in the discharge frequency. In 15% of the neurons there was an increased frequency of firing. Eleven percent of the neurons exhibited a mixed response consisting of an initial depression of discharge rate followed by a delayed increase. The responses of STN neurons to DA were not antagonized by iontophoretically applied haloperidol. In neurons whose firing frequency was decreased by DA, the iontophoretic application of apomorphine and norepinephrine also decreased discharge rate. The observations of HRP-labelled neurons in the pars compacta region of substantia nigra following injection of HRP into the STN together with the DA responsiveness of STN neurons suggest the possibility of a dopaminergic nigro-subthalamic pathway.