Biomedical subjects

S T Kitai

Publications and source records attributed to S T Kitai.

At least 37 records · Page 2Linked to original sources

PubMed1997

State-dependent regulation of neuronal excitability by dopamine.

Since the discovery that the loss of the dopaminergic innervation of the striatum resulted in Parkinson's disease, physiologists have attempted to understand the role of dopamine on striatal activity. Hypotheses relying upon concepts derived from studies of fast synaptic transmission have consistently failed to explain the actions of dopamine or other receptors coupled to G-proteins which modulate the properties of voltage-dependent ionic conductances responsible for synaptic integration and spike activity. Recently, patch clamp studies have revealed that in medium spiny striatal neurons dopamine D1-class receptors modulate voltage-dependent Na+, K+ and Ca2+ channels. From a consideration of the biophysical properties of these channels and the state transitions that medium spiny neurons undergo while responding to cortical input, a novel picture of dopamine's actions is beginning to emerge. Our results and those of others suggest that D2-class receptors serve to make the transition to the depolarized 'upstate' from the hyperpolarized 'downstate' more probable in response to cortical input. But, once the transition has occurred, the alteration in excitability should be short-lived unless the neuron has recently been active. This state-dependent modulation provides a mechanism by which dopamine could shape global striatal activity governing the execution of motor behaviors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1996

Cholinergic and noncholinergic tegmental pedunculopontine projection neurons in rats revealed by intracellular labeling.

Morphological features of rat pedunculopontine projection neurons were investigated in in vitro preparation by using intracellular labeling with biocytin combined with choline acetyltransferase (ChAT) immunohistochemistry. These neurons were classified into two types (Type I and II), based on their electrical membrane properties: Type I had low-threshold Ca2+ spikes, and Type II had A-current. All Type I neurons (n = 17) were ChAT immunonegative (ChAT-). Type II neurons were either ChAT immunopositive (ChAT+; n = 49) or ChAT- (n = 20). In terms of topography in the tegmental pedunculopontine nucleus (PPN), Type I neurons were dispersed throughout the extent of the nucleus, whereas Type II neurons tended to be located more in the rostral and middle sections. Both Type I and II neurons consisted of small (long axis < 20 microns), medium (20-35 microns), and large (> 35 microns) cells. The small cells were round or oval; medium cells were round, triangular, or fusiform; and the large cells were primarily fusiform in shape. In terms of the soma size, there was a difference in Type I (15-38 microns) and Type II (11-50 microns) neurons, but no significant difference was found between Type II ChAT+ and ChAT- cells. Both types of neurons had three to six primary dendrites, but the dendritic field was more prominent in Type II neurons. Most of the axons originated from one of the primary dendrites, which gave off axon collaterals, some of which projected out of the nucleus. The intrinsic collaterals were thin and branched partly within the dendritic field of the parent cell. The extrinsic collaterals were thicker and could be grouped into three categories: 1) collaterals arborizing in the substantia nigra; 2) collaterals ascending mainly toward the thalamus, pretectal, and tectal area; and 3) collaterals descending toward the mesencephalic and/or pontine reticular formation. It was noted that the collaterals of both ChAT+ and ChAT-neurons were traced into the substantia nigra. There was no significant difference in antidromic latencies between Type I (m = 1.47 msec) and Type II (m = 1.36 msec) neurons following electrical stimulation of the substantia nigra.

Animals↗

PubMed1996

Organotypic cortex-striatum-mesencephalon cultures: the nigrostriatal pathway.

We were successful in developing cortex-striatum-mesencephalon organotypic cultures from the rat brain after 4-9 weeks in vitro. A modification of the 'roller tube' technique was employed where slices were embedded in a plasma/thrombin clot onto a Millicell membrane on a coverslip. The underlying membrane provided high mechanical stability during culturing, which reduced the likelihood of deterioration of the cultures. Tyrosine hydroxylase immunoreactivity was used to label dopamine neurons and axonal innervation into the cortical and striatal culture. The electrophysiological responses of striatal medium-sized spiny neurons to cortical, striatal and mesencephalic stimulation were characterized.

Animals↗

PubMed1996

Partial striatal dopamine depletion differentially affects striatal substance P and enkephalin messenger RNA expression.

Near total striatal dopamine denervation results in a decrease in substance P and an increase in enkephalin messenger RNA expression in the striatum. It is unknown whether partial depletions of striatal dopamine content produce similar changes in these peptide messenger RNAs. To test whether compensations in dopamine synthesis and release following partial dopamine denervation prevent the lesion-induced alterations in substance P and enkephalin messenger RNAs, varying concentrations of 6-hydroxydopamine were injected unilaterally into the substantia nigra. Seven days after injection of 6-hydroxydopamine (2-16 micrograms) or vehicle, in situ hybridization histochemistry was used to examine tyrosine hydroxylase messenger RNA in the substantia nigra and substance P and enkephalin messenger RNAs in the striatum. The extent of the dopamine depletion was determined by measuring striatal dopamine tissue content. The decrease in tyrosine hydroxylase messenger RNA paralleled the change in striatal tissue dopamine content. Substance P messenger RNA was decreased in all lesioned rats. In contrast, a significant increase in enkephalin messenger RNA was not detected until striatal dopamine was reduced to 10% of control levels. These results suggest that compensations within the residual dopamine system are not sufficient to maintain normal striatal substance P messenger RNA levels in partially denervated animals, but are sufficient to maintain normal striatal enkephalin messenger RNA expression.

Animals↗

PubMed1996

Generation of high-frequency oscillations in local circuits of rat somatosensory cortex cultures.

1. Rhythmic cortical activity was investigated with intracellular recordings in cortex-striatum-mesencephalon organotypic cultures grown for 42 +/- 3 (SE) days in vitro. 2. Electrical stimulation of supragranular layers induced a self-sustained high-frequency oscillation (HFO) in pyramidal neurons and interneurons. 3. The HFO started 197 +/- 39 ms after stimulation and had a mean duration of 1.0 +/- 0.2 s and an initial frequency of 38 +/- 2 Hz. A decrease in frequency at a rate of 11.5 +/- 2.7 Hz/s started on average 547 +/- 109 ms after the onset of the HFO. 4. During the HFO, local interneurons and pyramidal neurons synchronized their activities. The synaptic origin of the HFO was confirmed by its reversal potential at -57 +/- 4 mV. 5. These results suggest that a self-maintained HFO can be induced in local cortical circuits by excitation of supragranular layers. This HFO would facilitate synchronization between distant cortical and thalamic regions.

Animals↗

PubMed1995

Developmental expression of KG-CAM in the rat neostriatum.

The present study examines the developmentally regulated expression pattern of an Ig superfamily member, KG-CAM, in the neostriatum of the rat. KG-CAM is a 90-kDa glycoprotein that is related to the DM-GRASP/Neurolin family of adhesion molecules. In the embryonic and early postnatal neostriatum, the distribution of KG-CAM correlates with the distribution of dopaminergic terminals. Early in neostriatal development, KG-CAM is found in the tyrosine hydroxylase-positive patches. In the maturing neostriatum, the levels of KG-CAM remain high within the patches, and KG-CAM upregulates in the matrix compartment. As the neostriatum is reaching its adult morphology, 5 weeks postnatal, the expression of KG-CAM in the matrix is approximately equal to that of the patches. When the distribution of KG-CAM is examined at the ultrastructural level, the immunoreactivity is localized to the external surface of neuronal and glial profiles in the neuropil. KG-CAM does not appear to be associated with the guidance of dopaminergic axons from the substantia nigra to the striatum, for this pathway is not immunopositive for this member of the Ig superfamily. The present study identifies an Ig superfamily member, KG-CAM, that appears to play a major role in the development of the neostriatum. Furthermore, the high levels of KG-CAM in the adult neostriatum suggest that this Ig superfamily member may be involved in maintaining the integrity of this structure in the adult rat.

Activated-Leukocyte Cell Adhesion Molecule↗

PubMed1995

Glutamatergic and cholinergic inputs from the pedunculopontine tegmental nucleus to dopamine neurons in the substantia nigra pars compacta.

Postsynaptic responses of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) to stimulation of the pedunculopontine tegmental nuclei (PPN) were studied in in vitro slice preparations in the rat. The recorded neurons were intracellularly injected with biocytin and also identified as DA neurons by an immunocytochemical technique. PPN stimulation induced in DA neurons monosynaptic excitatory postsynaptic potentials (EPSPs) that consisted of early transient and slow components. An application of anti-glutamatergic agents (1 mM kynurenic acid and/or 30 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)) in the bathing media partially suppressed the EPSPs, indicating that PPN inputs to SNc DA neurons are glutamatergic and non-glutamatergic. Anti-glutamatergic resistant EPSPs were suppressed by applications of anti-cholinergic agents such as atropine, mecamylamine, and pirenzepine. These data indicate a convergence of glutamatergic and cholinergic excitatory inputs from the PPN to SNc DA neurons and that both nicotinic and muscarinic receptors are involved in the cholinergic transmission.

Acetylcholine↗

PubMed1994

The morphology of globus pallidus projection neurons in the rat: an intracellular staining study.

The morphology of 23 intracellularly stained projection neurons of rat globus pallidus (GP) was studied in light microscopic preparations. The somatic size of these projection neurons was highly variable. The somatic area ranged from 78 to 353 microns 2. The 23 neurons were divided into aspiny and spiny types, based on the existence of dendritic spines. Sixteen neurons were aspiny and 7 were of the spiny type. The aspiny neurons tended to have a larger soma than the spiny neurons. Fourteen of the 23 projection neurons possessed a discoidal dendritic field with the flat plane parallel to the border between the GP and the neostriatum. All of the 14 neurons having a discoidal dendritic field were of the aspiny type and were located throughout the GP. The other 9 neurons, which include all of the 7 spiny types, had radiating dendritic fields with a variety of shapes and were located only in the medial region of the GP. The axons of a majority (i.e. 21 of 23) of the projection neurons emitted multiple collaterals with large boutons en-passant and boutons terminaux within the GP. The main axons were traced to varying distances from their somata. Four of them were traced into the substantia nigra. Two of these 4 emitted multiple collaterals at various rostro-caudal levels in the entopeduncular nucleus, and all 4 axons had one or two collaterals in the subthalamic nucleus. This study revealed that the rat GP contains two types of projection neurons having different dendritic morphologies. The axon reconstructions indicate that the activity of both types of neurons can influence multiple basal ganglia targets, including the GP itself.

Animals↗

PubMed1994

Temporal dissociation between changes in striatal enkephalin and substance P messenger RNAs following striatal dopamine depletion.

Changes in the levels of enkephalin and substance P messenger RNA expression were examined in the striatum following dopamine depletion resulting from unilateral injection of 6-hydroxydopamine into the substantia nigra. In response to striatal dopamine depletion, the levels of enkephalin messenger RNA were elevated, whereas substance P messenger RNA was decreased within all regions of the striatum. Examination of the striatal peptide messenger RNAs between one and 21 days after the injection of 6-hydroxydopamine revealed a temporal dissociation between changes in enkephalin and substance P messenger RNAs. Within one day of the 6-hydroxydopamine injection, substance P messenger RNA was significantly decreased by 30% at all levels of the striatum. This decrease was maintained for up to 21 days after the lesion. In contrast, striatal enkephalin messenger RNA was not significantly elevated until three days following the injection of 6-hydroxydopamine, after which there was a gradual increase up to 21 days. In order to correlate alterations in peptide messenger RNA expression with 6-hydroxydopamine-induced changes in striatal dopamine innervation, tissue punches from the striatum were examined for dopamine content at one, two, three and seven days after the lesion. One day after the lesion, striatal dopamine levels were significantly increased by 47%. In contrast, within two days tissue dopamine content was reduced by 77% compared to control levels. A further decrease of 90% or more was observed at three and seven days after the lesion. Taken together, these data demonstrate a temporal dissociation between changes in enkephalin and substance P messenger RNA levels following 6-hydroxydopamine-induced striatal dopamine depletions. This temporal dissociation may reflect a differential response of enkephalin and substance P messenger RNAs to alterations in dopamine release and subsequent receptor activation.

Animals↗

PubMed1994

Dopaminergic and muscarinic regulation of striatal enkephalin and substance P messenger RNAs following striatal dopamine denervation: effects of systemic and central administration of quinpirole and scopolamine.

Striatal dopamine depletion produces an increase in enkephalin and a decrease in substance P messenger RNAs. Subsequent systemic administration of either the D2 dopamine agonist, quinpirole, or the muscarinic antagonist, scopolamine, results in the reduction of the lesion-induced elevation in striatal enkephalin messenger RNA. These changes in enkephalin messenger RNA levels may be mediated solely within the striatum or through trans-synaptic circuits involving the striatum. To dissociate these possibilities, we have compared the effects of systemic and central administration of quinpirole and scopolamine on striatal enkephalin and substance P messenger RNAs using in situ hybridization histochemistry. Systemic administration of both quinpirole and scopolamine blocked the elevation of striatal enkephalin messenger RNA normally observed in 6-hydroxydopamine-lesioned rats. In addition, high doses of systemic scopolamine (25 and 50 mg/kg per day) prevented the lesion-induced decrease in striatal substance P messenger RNA levels. In order to determine whether the effects of these drugs are mediated directly within the striatum, central administration of quinpirole and scopolamine were compared. In contrast to systemic administration, intraventricular and intrastriatal infusion of quinpirole but not scopolamine prevented the lesion-induced change in striatal enkephalin messenger RNA. However, neither quinpirole nor scopolamine administered centrally affected the level of substance P messenger RNA in the striatum of 6-hydroxydopamine-induced lesioned animals. Together, these data suggest that changes in D2 receptor activation directly in the striatum are responsible for the effects of quinpirole on enkephalin messenger RNA. In contrast, the effect of systemic scopolamine on striatal enkephalin and substance P messenger RNAs may not be mediated within the striatum.

Animals↗

PubMed1994

Dopaminergic regulation of striatal efferent pathways.

In the past year there has been a growing debate about the distribution of dopamine receptors in striatal efferent pathways. As is often the case, different approaches lead to different perspectives. Nevertheless, the available data can be reconciled with a model in which D1 and D2 dopamine receptors are segregated in the distal dendrites and axonal terminal fields of striatonigral and striatopallidal neurons, but intermingled in the soma and proximal dendrites.

Animals↗

PubMed1994

Acutely isolated neurons of the rat globus pallidus exhibit four types of high-voltage-activated Ca2+ current.

1. Large, projection-like neurons from the adult (> 3 wk post-natal) rat globus pallidus (GP) were acutely isolated and subjected to whole-cell voltage-clamp (n = 37). Ca2+ currents were isolated pharmacologically in cells with whole-cell capacitances of 15-34 pF. 2. With 5 mM Ba2+ as a charge carrier, whole-cell currents began to activate near -40 mV and peaked near 0 mV. Based on activation threshold and inactivation kinetics, currents appeared to be of the high-voltage-activated type. 3. Cd2+ blocked whole-cell currents with an IC50 near 2 microM. Currents activated at negative potentials were not relatively resistant to Cd2+, supporting the inference that low-voltage-activated currents were not prominent in these neurons. 4. The dihydropyridine, L-channel antagonist, nifedipine (5 microM), reduced peak current by 21 +/- 4% (SD) (n = 10). The dihydropyridine agonist, BayK 8644 (1-2 microM) enhanced peak current and slowed current deactivation (n = 4). 5. The N-channel antagonist, omega-conotoxin GVIA (omega-CgTx, 2 microM) blocked 25 +/- 7% of the peak whole-cell current (n = 10). The blocks produced by omega-CgTx and nifedipine were additive, blocking an average of 46 +/- 8% of the current (n = 10). 6. The current resistant to the selective N- and L-channel antagonists was partially blocked by the P-channel antagonist omega-agatoxin IVA (omega-AgTx, 100 nM). omega-AgTx blocked about one-half of the current not attributable to N- and L-type channels (22 +/- 5% of the total current, n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Somatostatin- and substance P-like immunoreactivity in rat neostriatal cultures.

In the normal adult neostriatum, somatostatin immunoreactive interneurons constitute a few percent of the total neuronal population whereas substance P immunoreactive neurons, which project to the substantia nigra, constitute nearly half of the total. Primary monolayer neostriatal cultures derived from E17 rat brains displayed both somatostatin-like and substance P-like immunoreactivity (SOM-IR and SP-IR). However, the proportions of SOM-IR and SP-IR neurons in vitro were significantly different from those in vivo. At 4 days in vitro (DIV), SOM-IR neurons comprised 19% of all neurons and this percentage increased to 30% at 25 DIV. In contrast, SP-IR neurons were less common than expected at 4 DIV (20%) and declined in percentage to 13% at 27 DIV. These results suggest that survival in target-deprived neostriatal cultures is favored for SOM-IR interneurons.

Animals↗

PubMed1993

Calcium spike underlying rhythmic firing in dopaminergic neurons of the rat substantia nigra.

In order to study a possible mechanism for rhythmic firing of dopaminergic (DA) neurons, intracellular recordings were obtained from 56 rhythmically firing DA neurons in the rat substantia nigra compacta (SNc), using in vitro slice preparations. In the presence of TTX, spontaneous oscillation of the membrane potential was induced in SNc DA neurons when the membrane potential was depolarized more positive from -60 to -40 mV. Each oscillation wave was characterized by a pacemaker-like slow depolarization (PLSD) followed by a relatively prompt repolarization. As the DC depolarization was increased from -60 to -40 mV, the oscillation frequency increased from 0.5 to 5 Hz, but the amplitude of the wave decreased. Of 17 neurons tested in the presence of TTX, the maximum amplitudes of the oscillation varied from 10-15 mV in 8 neurons and were less than 5 mV in 9 neurons. In those 9 neurons, an application of TEA greatly enhanced (up to 15 mV) the amplitude of oscillation. The oscillation ceased when the membrane was hyperpolarized more negative than -60 mV. At the membrane potential more negative than -60 mV in the presence of TTX an injection of a depolarizing current pulse could evoke PLSD which was an all-or-nothing regenerative spike potential. The rate of rise of the PLSD changed depending on the intensity of injected current pulses but their amplitude remained constant. Its time-to-peak was slow (up to 1400 ms), while the decay time was relatively brief (< 500 ms). The threshold membrane potential for evoking PLSD was -53.7 +/- 3.2 mV (n = 10). This was higher than the previously reputed threshold for low threshold Ca2+ spike (LTS) (< -60 mV) and lower than that for high threshold Ca2+ spike (HTS) (> -35 mV) in SNc DA neurons. Even at a holding potential of -45 mV, a depolarizing current pulse could trigger PLSD while LTS was completely inactivated. Cd2+ (0.4 mM) abolished the oscillation and PLSD without marked effects on the LTS (n = 6). A low Ca2+ and high Mg2+ Ringer's solution also abolished the oscillation and PLSD (n = 4). An intracellular injection of EGTA markedly prolonged the decay time course of PLSD characterized by a slow and a relatively fast falling phase (n = 5). This would suggest an involvement of Ca(2+)-dependent K+ conductance and/or Ca2+ dependent inactivation of Ca2+ conductance during repolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1993

A whole cell patch-clamp study on the pacemaker potential in dopaminergic neurons of rat substantia nigra compacta.

A whole-cell patch-clamp recording was obtained from dopamine (DA) neurons (n = 68) in the substantia nigra compacta (SNc) in in vitro slice preparations in order to study the underlying current for pacemaker-like slow depolarization (PLSD) which was considered as a basis for rhythmic firing of DA neurons. SNc DA neurons were identified immunohistochemically after recording. Results demonstrated that: (1) Under current clamped condition in the presence of TTX, DA neurons (n = 5) displayed the oscillation of membrane potential with high threshold spikes. An application of a hyperpolarizing and depolarizing current pulse (at the membrane potential where oscillation was no longer seen) induced a prominent anomalous rectification and pacemaker-like slow depolarization (PLSD), respectively. (2) Under voltage-clamped conditions in the presence of TTX, a command pulse positive to -50 mV from a holding potential of -80 mV induced a persistent Ca2+ current which was usually preceded by either a transient K+ (n = 7) or a transient Ca2+ (n = 4) current recorded with a patch pipette containing potassium gluconate (145 mM). (3) When outward currents were suppressed by 140 mM CsCl and 10 mM EGTA intercellularly applied through the patch pipette, a command pulse positive to -50 to -40 mV induced either a persistent Ca2+ current alone (n = 4) or a persistent Ca2+ current preceded by a transient Ca2+ current (n = 11). (4) The threshold for activation of the persistent Ca2+ current (Ip) was around -60 to -55 mV. The amplitude of Ip produced by a command pulse stepped to -50 mV from a holding potential of -80 mV was -78 +/- 42 pA (n = 23). (5) The threshold for activation of transient Ca2+ current (IT) was around -70 to -65 mV and inactivated completely at -70 to -65 mV (n = 11). The peak amplitude of IT evoked at -60 to -55 mV from a holding potential of more negative than -80 mV was 489 +/- 170 pA (n = 11). (6) The decay time constant of IT was 28 +/- 12 ms at -60 mV (n = 8) and that of IP was 2.35 +/- 1.37 s at -50 mV (n = 11) when recorded with a pipette containing 10 mM EGTA and 140 mM CsCl. (7) The decay of IP was apparently accelerated by decreasing the concentration of EGTA in the pipette solution from 10 to 1 mM.(ABSTRACT TRUNCATED AT 400 WORDS)

Amplifiers, Electronic↗

PubMed1993

D1 and D2 dopamine receptor modulation of sodium and potassium currents in rat neostriatal neurons.

The potassium and sodium currents in acutely isolated neostriatal neurons are modulated by activation of both D1- and D2-class receptors. The amplification of mRNA in individual neurons supports this conclusion and has shown that striatonigral neurons express not only D1 and D2 receptors, but D3 receptors as well. The characteristics of the modulations produced by these receptors provide a foundation for both antagonistic and synergistic actions of D1 and D2 agonists in the neostriatum. Understanding precisely how these modulations interact in shaping excitability, however, will require a better characterization of spatial domains in which they operate.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1993

Cholinergic and dopaminergic modulation of potassium conductances in neostriatal neurons.

Muscarinic and dopaminergic ligands exert their principal effects on excitability by modulating voltage-dependent conductances. Potassium currents activated by depolarization are among the conductances modulated. These currents can be divided into rapidly (Af) and slowly inactivating (A(s)) A-currents and a delayed rectifier current. The voltage-dependence and maximal conductance of the Af current are modulated by muscarinic agonists, presumably through a M1 receptor. This pharmacological class of receptors is coupled to phosphoinositide hydrolysis as well as the inhibition of cAMP accumulation. The nature of the muscarinic modulation of the Af current suggests that acetylcholine should not be viewed as excitatory or inhibitory but rather as enhancing state stability. Dopaminergic agonists appear to selectively modulate the A(s) current, rather than the Af current. This current is expressed late in the postnatal development of neostriatal neurons and plays an important part in regulating integrative behavior. Both D1 and D2 receptors mediate dopaminergic modulation. D1 agonists suppress this current whereas D2 agonists enhance it. The interaction of the dopaminergic modulation with the state transitions medium spiny neurons undergo in generating spike activity has yet to be fully explored. Nevertheless, it is clear that the modulation of the A(s) current provides a basis on which dopamine might interact with acetylcholine in controlling neostriatal excitability.

Acetylcholine↗

PubMed1992

Dopamine receptor subtypes colocalize in rat striatonigral neurons.

Dopaminergic neurons of the substantia nigra provide one of the major neuromodulatory inputs to the neostriatum. Recent in situ hybridization experiments have suggested that postsynaptic dopamine receptors are segregated in striatonigral and striatopallidal neurons. We have tested this hypothesis in acutely isolated, retrogradely labeled striatonigral neurons by examining the neuromodulatory effects of selective dopaminergic agonists on Na currents and by probing single-cell antisense RNA populations with dopamine receptor cDNAs. In most of the neurons examined (20/31), the application of the D1 dopamine receptor agonist SKF 38393 reduced evoked whole-cell Na+ current. The D2 agonists quinpirole and bromocriptine had mixed effects; in most neurons (23/42), whole-cell Na+ currents were reduced, but in others (8/42), currents were increased. In cell-attached patch recordings, bath application of SKF 38393 decreased currents as in whole-cell recordings, whereas quinpirole consistently (6/10) enhanced currents--suggesting that D2-like receptors could act through membrane delimited and non-delimited pathways. Changes in evoked current were produced by modulation of peak conductance and modest shifts in the voltage dependence of steady-state inactivation. Antisense RNA probes of dopamine receptor cDNA Southern blots consistently (5/5) revealed the presence of D1, D2, and D3 receptor mRNA in single striatonigral neurons. These findings argue that, contrary to a strict receptor segregation hypothesis, many striatonigral neurons colocalize functional D1, D2, and D3 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗