Decortication decreases paired-pulse facilitation in the neostriatal slice of the rat.

Paired-pulse facilitation, a form of short-term synaptic enhancement, occurs in the neostriatum. The present experiments were designed to determine the contributions of neostriatal afferents to the maintenance of this form of short-term facilitation. There are 3 major afferents to the neostriatum: the neocortex, the substantia nigra and the medial thalamus. Since the largest inputs into the neostriatum emanate from the neocortex and substantia nigra, the effects of unilateral decortication or unilateral dopamine depletion on paired-pulse facilitation were primarily examined. Intracellular recordings were made from neostriatal neurons in brain slices 2 weeks following unilateral decortication or dopamine-depleting lesions. Statistically significant decreases in paired-pulse facilitation of the synaptic response evoked by local stimulation occurred only after neocortical damage. In contrast, paired-pulse facilitation in neostriatal neurons ipsilateral to the dopamine depleting lesion was not significantly altered. These results indicate that the corticostriatal input is primarily responsible for neostriatal short-term synaptic facilitation.

Norepinephrine modulates excitatory amino acid-induced responses in developing human and adult rat cerebral cortex.

These experiments were designed to assess the ability of norepinephrine and its beta-receptor agonist, isoproterenol, to modulate responses induced by activation of excitatory amino acid receptors in brain slices obtained from developing human cortex or adult rat cortex. Human cortical slices were obtained from children undergoing surgery for intractable epilepsy (9 months to 10 yr of age). For comparison, slices were also obtained from rats (2-3 months of age). Iontophoretic application of glutamate, N-methyl-D-aspartate or alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) produced excitatory responses consisting of membrane depolarizations accompanied by action potentials. Iontophoretic or bath application of norepinephrine or isoproterenol enhanced responses evoked by glutamate or N-methyl-D-aspartate. Depolarizations occurred with shorter latencies and their amplitudes increased. Action potential frequency was also increased and responses were of longer duration. In contrast, norepinephrine or isoproterenol had no effect on responses induced by AMPA. The enhancement of responses induced by N-methyl-D-aspartate or glutamate was antagonized by the beta-adrenergic receptor antagonist propranolol. Similar findings were obtained from neurons in humans or rats. These results suggest that norepinephrine, possibly via beta-receptors, potentiates responses mediated by glutamate and N-methyl-D-aspartate receptors without affecting those mediated by AMPA receptors. These effects were observed at all ages studied, indicating that the ability of norepinephrine to modulate excitatory neuronal transmission is well developed in human cortex by 9 months of age.

Neurophysiological, pharmacological and morphological properties of human caudate neurons recorded in vitro.

Tissue samples from the caudate nucleus were obtained from eight children (eight to 172 months of age) who underwent hemispherectomies for the relief of intractable seizures. Neurophysiological, pharmacological and morphological properties of caudate neurons were characterized by intracellular recordings in an in vitro slice preparation. These properties were compared with those of tissue obtained from animal studies. Electrophysiological properties of human caudate neurons that were similar to those of cat caudate and rat neostriatal cells included resting membrane potential, input resistance, action potential rise time, fall time, duration and action potential afterhyperpolarization amplitude, as well as the general characteristics of locally evoked synaptic responses. Properties that were different included action potential amplitudes and time-constants. Human caudate neurons also displayed responses similar to those of cat caudate or rat neostriatal cells to manipulation of excitatory amino acid receptor systems and to dopamine application. Kynurenic acid, a broad-spectrum excitatory amino acid receptor antagonist, decreased the amplitude of evoked synaptic responses, indicating that they were partially mediated by excitatory amino acids. In Mg2+ free Ringer's solution, the amplitudes and durations of postsynaptic responses were increased and bursts of action potentials were induced. These effects were mediated by activation of N-methyl-D-aspartate receptors since they were blocked by 2-amino-5-phosphonovalerate, a specific N-methyl-D-aspartate-receptor antagonist. Iontophoretic application of N-methyl-D-aspartate also induced membrane oscillations and bursts in almost all caudate neurons. Dopamine decreased the amplitude of postsynaptic responses, an effect antagonized by domperidone, a selective D2 dopamine receptor antagonist. Developmentally, the greatest change was an increase in action potential amplitude, although input resistance decreased and action potential afterhyperpolarization amplitude increased. Postsynaptic responses were similar across age. All but one of the caudate neurons identified by intracellular injection of biocytin or Lucifer Yellow were medium-sized spiny cells. These experiments show that human caudate neurons display a number of electrophysiological properties similar to rat neostriatal or cat caudate neurons recorded in brain slices. Furthermore, few electrophysiological parameters changed significantly over the age period examined suggesting that the human caudate at eight months displays many of the neuronal functions of the more mature caudate nucleus.

Evidence for enhanced synaptic excitation in transplanted neostriatal neurons.

Fetal neostriatal tissue was transplanted into either the neostriatum or substantia nigra of adult rats. One to 6 months after transplantation, coronal brain slices were taken through the rostrocaudal extent of the transplants and neurons were characterized electrophysiologically using an in vitro slice preparation. When compared to control neurons taken from intact adult neostriata, transplanted neostriatal neurons (TSNs) had higher input resistances and longer time constants. All other passive and active membrane properties assessed were comparable between transplanted and control neostriatal neurons. Regardless of the transplantation site, local extracellular stimulation outside the graft elicited high-amplitude, long-duration depolarizing synaptic potentials that typically triggered bursts of action potentials. These synaptic potentials contrast with lower amplitude, shorter duration synaptic potentials consistently elicited in control neostriatal neurons. The depolarizing synaptic potentials evoked in the TSNs appeared to be mediated by a combined activation of N-methyl-D-aspartate (NMDA) and non-NMDA excitatory amino acid receptors. Both the broad-spectrum excitatory amino acid antagonist kynurenic acid and the specific non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione significantly reduced postsynaptic potentials elicited in TSNs. The specific NMDA antagonist 2-amino-5-phosphonovalerate had less effect on the amplitude but markedly reduced the duration of the synaptic potentials. The duration and amplitude of the bursts were augmented by the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide, indicating that inhibition occurred in TSNs. TSNs were also more sensitive than control neurons to direct application of glutamate or NMDA. These findings demonstrate that TSNs express altered electrophysiological properties. The pharmacological analysis indicates that depolarizing postsynaptic potentials were mediated by activation of excitatory amino acid receptors, suggesting either innervation of the graft by host fibers which contain excitatory amino acids or development of novel local excitatory interactions intrinsic to the graft. Furthermore, the occurrence of high-amplitude, long-duration depolarizing synaptic potentials in TSNs, regardless of the site of transplantation, suggests that grafted neostriatal neurons become hyperexcitable to synaptic input.

Neuromodulatory actions of dopamine in the neostriatum are dependent upon the excitatory amino acid receptor subtypes activated.

In the mammalian neostriatum, dopamine modulates neuronal responses mediated by activation of excitatory amino acid receptors. The direction of this modulation varies with the specific subtype of excitatory amino acid receptor activated. Responses evoked by iontophoretic application of glutamate (Glu) and the non-N-methyl-D-aspartate (NMDA) agonists quisqualate and alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid were significantly attenuated when dopamine was applied. In contrast, responses evoked by NMDA were markedly potentiated. The enhancement of NMDA-evoked excitations was mimicked by bath application of SKF 38393, a D1 receptor agonist. The D1 receptor antagonist SCH 23390 blocked the dopamine enhancement of NMDA-induced excitations. Quinpirole, a D2 receptor agonist, attenuated responses evoked by both NMDA and non-NMDA receptor agonists. These results indicate that the complex modulatory actions of dopamine in the neostriatum are a function of the excitatory amino acid receptor as well as the specific dopamine receptor subtype activated. These findings are of clinical relevance since the actions of dopamine and excitatory amino acids have been implicated in neurological and affective disorders.

Dye-coupling in human neocortical tissue resected from children with intractable epilepsy.

Interneuronal communication mediated by gap junctions has been proposed to have an important role in brain development and in the genesis of epilepsy. Indirect evidence for the existence and function of gap junctions has been obtained by studying dye-coupling, the transfer of the low-molecular-weight fluorescent dye Lucifer yellow (LY), among neurons. In the present study, the incidence of dye-coupling was assessed at different stages of human postnatal brain development. Pathological neocortical tissue was obtained from children from 3 to 172 months of age suffering from pediatric epilepsy and undergoing surgery to alleviate intractable seizures. Tissue samples were classified into least and most abnormal according to a number of diagnostic measures to ascertain if the incidence of dye-coupling could be related to the degree of epileptogenicity of the sample. Regardless of the degree of abnormality, a significant developmental decrease in the incidence of dye-coupling was observed. In children 3-16 months, dye-coupling occurred in 38% of single intracellular injections of LY. From 32 to 83 months, the frequency of dye-coupling decreased to 13%. Finally, from 93 to 172 months, dye-coupling was observed in only 4% of injections. The frequency of dye-coupling between the least and most abnormal samples was not significantly different, although the frequency of dye-coupling was higher in the least abnormal samples from the youngest group (3-16 months). These findings underscore the role of gap junctions during brain development. However, they do not provide support, at least in vitro, for the hypothesis that gap junctions have an important role underlying epilepsy.

Age-induced changes in electrophysiological responses of neostriatal neurons recorded in vitro.

The present studies were undertaken to determine whether the major electrophysiological characteristics of neostriatal neurons are altered during aging. The passive and active membrane properties of 130 neostriatal neurons obtained from young (three to five months, N = 65) and aged (24-26 months, N = 65) Fischer 344 rats were compared using an in vitro slice preparation. The results indicated that in a population of aged neostriatal neurons the majority of the electrophysiological changes that occurred resulted in decreases in cellular excitability. These changes included increased threshold to induce action potentials by intracellular current injection and decreased negativity of membrane potentials at which such action potentials were induced. In addition, there were increases in the amplitude of the action potential afterhyperpolarization and increases in the frequency of occurrence of accommodation when trains of action potentials were induced. These two latter effects can limit the frequency of action potential generation. The thresholds to elicit synaptically evoked depolarizing responses and action potentials were increased. The results also indicated that a number of basic electrophysiological parameters were unchanged by the aging process. These included action potential amplitude, rise time and duration, resting membrane potential, input resistance and time constant. Although thresholds for the induction of synaptic and action potentials by extracellular stimulation were increased, the latency, amplitude and duration of the evoked depolarization remained unchanged. These findings suggest that the ability of neostriatal neurons to integrate spatiotemporal inputs must be severely compromised in this population of aged cells. Furthermore, the present findings, when compared with age-induced electrophysiological alterations in neurons in other brain areas, indicate that age may differentially alter electrophysiological properties of neurons in separate nuclei. Profiles of age-related changes in neurophysiological properties of neurons provide important information that can be related to the contributions of individual neural areas to the behavioral effects of aging.

Differential modulation by dopamine of responses evoked by excitatory amino acids in human cortex.

The responses of human neocortical neurons to iontophoretic application of excitatory amino acids and their modulation by dopamine (DA) were studied in vitro. Brain slices were obtained from children undergoing surgery for intractable epilepsy. Application of N-methyl-D-aspartate (NMDA) to the slices induced slow depolarizations accompanied by decreased input conductances and sustained action potentials in cortical neurons. Glutamate produced rapid depolarizations and firing with few changes in input conductances. Quisqualate also induced depolarization and firing, but input conductances increased during the rising phase of the membrane depolarization. Iontophoretic application of DA alone produced no change in membrane potential or input conductance. However, when DA was applied in conjunction with the excitatory amino acids, it produced contrasting effects. With either bath application of DA or when iontophoresis of DA preceded application of NMDA, the amplitude of the membrane depolarizations and the number of action potentials were increased, whereas the latency of these responses decreased. In contrast, DA decreased the amplitude of the depolarizations and the number of action potentials evoked by glutamate or quisqualate. The fact that DA affects responses to NMDA and glutamate or quisqualate in opposite directions is of considerable importance to the understanding of cellular mechanisms of neuromodulation and the role of DA in cognitive processing and in epilepsy.

Enhanced responses to NMDA receptor activation in the developing cat caudate nucleus.

An in vitro slice preparation was used to assess the effects of N-methyl-D-aspartate (NMDA) receptor activation in the developing cat caudate nucleus. Removal of Mg2+ from the bathing medium, in the presence of 10 microM bicuculline, increased the amplitude and duration of the excitatory postsynaptic potential induced by local extracellular stimulation at all ages tested. In neurons younger than 35 days of age, removal of Mg2+ in the presence of bicuculline produced an increase in excitatory postsynaptic potential amplitude and duration as well as bursts of action potentials when local extracellular stimulation was applied. The effects of Mg2+ removal were reversibly attenuated by the specific NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid. These findings are important because they demonstrate that NMDA receptor-mediated responses can be induced in developing caudate neurons by local extracellular stimulation and these responses are enhanced in early postnatal periods at ages when motor control is being established.

Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat.

A mutant strain of Han-Wistar rat carries an autosomal recessive gene producing spastic paresis which is characterized by ataxia, tremor and hind limb rigidity. Brains of affected rats and unaffected littermate controls were transected at the mesencephalon into rostral and caudal portions (the caudal portion contained the cerebellum and brainstem). Poly(A)+ mRNA was isolated from pooled rostral or caudal portions and injected into Xenopus oocytes. The oocytes were voltage-clamped and exposed to 1 mM L-glutamate, 500 microM kainate, 500 microM quisqualate, 200 microM N-methyl-D-aspartate (NMDA) or 1 mM gamma-aminobutyric acid (GABA). Oocytes injected with mRNA isolated from the caudal portions of the affected rat brains exhibited statistically significant increases in glutamate and kainate peak current responses compared to oocytes injected with mRNA from other brain samples. No differences were noted in the responses of the groups when exposed to quisqualate, NMDA or GABA. Cerebellar and brain stem mRNA were also isolated separately in different groups of mutants and unaffected littermates. Only oocytes injected with cerebellar mRNA from mutants displayed statistically significant increases in responses to glutamate and kainate. In parallel morphological studies changes in the cerebellum of mutants were also observed. These consisted of a loss of Purkinje cells and an asymmetrical disarrangement of the granule cell layer of cerebellar cortex. Taken together, the physiological and morphological results suggest that alterations in glutamate/kainate receptors in the cerebellum are phenotypic manifestations of the Han-Wistar mutation. The results are consistent with the hypothesis that this mutant rat might serve as a model of glutamate/kainate excitotoxicity in the brain.

Iontophoretic application of NMDA produces different types of excitatory responses in developing human cortical and caudate neurons.

The effects of iontophoretically applied N-methyl-D-aspartate (NMDA) were assessed in human neocortical and caudate neurons. NMDA depolarized cell membranes, decreased input conductances and induced firing. The discharge patterns differed in the two areas studied. In neocortex, NMDA produced repetitive spikes or bursts. In caudate, it induced slow, rhythmic plateau depolarizations accompanied by an initial burst of action potentials, followed by low amplitude, long duration spikes. After hyperpolarizations were seen after each depolarization in the caudate. These variations in patterns of excitation may relate to differences in local circuits intrinsic to each region, and/or to membrane conductances specific to each type of cell.

Neurophysiological maturation of cat caudate neurons: evidence from in vitro studies.

The membrane properties and synaptic physiology of developing cat caudate (Cd) nucleus neurons were studied in in vitro slice preparations. Recordings were obtained from 98 cells in kittens from fetal day (F) 56 to postnatal day (P) 90. With increasing age, the following maturational changes occurred; resting membrane potentials became more negative, action potential rise times decreased, action potential amplitudes increased, and action potential durations and input resistances decreased. The frequency of occurrence of afterhyperpolarizations and of anomalous rectification increased with age. The primary response to local extracellular stimulation was a depolarization usually accompanied by an action potential. Evoked hyperpolarizing responses were seen after P28 but only occurred if the membrane was depolarized by intracellular current injection. Cells identified by intracellular injection of Lucifer yellow were primarily medium-sized spiny neurons although it was not always possible to determine the cell type in slices from animals less than P5. Somatic diameter, dendritic length, and spine density increased with age. Dye-coupling occurred in slices less than P20. Its frequency decreased with age. These results show that Cd neurons undergo significant maturation during late prenatal and early postnatal periods. In contrast, substantia nigra neurons mature more rapidly and should be capable of influencing the less mature Cd neurons during development.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurophysiological maturation of cat substantia nigra neurons: evidence from in vitro studies.

The membrane properties and synaptic physiology of developing cat substantia nigra (SN) neurons were studied in in vitro slice preparations. Stable intracellular recordings were obtained from 46 neurons in 20 kittens ranging in age from fetal day (F) 51 to postnatal day (P) 120. Only two of these properties changed with development. The percentage of cells displaying inward rectification and the percentage of cells that generated low-threshold Ca++ spikes increased with age. Properties that did not change included resting membrane potentials, action potential amplitudes and durations, and input resistances. At all ages locally evoked synaptic responses consisted of sequences of excitatory postsynaptic potentials followed by inhibitory postsynaptic potentials. Most of the cells recorded had the electrophysiological properties which have been attributed to SN dopamine-containing neurons. To identify neurons morphologically, and verify the recording site, cells were filled with Lucifer yellow at the end of each experiment. Somatic shapes varied widely from oval to fusiform to triangular. Somatic diameters and dendritic length increased with development. Filopodial processes and growth cones were present up to the first postnatal month. Dye-coupling occurred only in the fetal group. These results indicate that cat SN neurons have many mature physiological properties during late fetal and early postnatal development. This contrasts with the significant maturation that occurs in cat caudate neurons during the same developmental period.

Synaptic transmission in human neocortex removed for treatment of intractable epilepsy in children.

Synaptic transmission to pyramidal cells was studied in slices of neocortex resected from infants and children (n = 10, age 8 months to 13 years) undergoing surgical treatment for intractable epilepsy. Most specimens were from the least abnormal area of the resection. Stable intracellular recordings could be obtained for up to 8 hours. Most of the recorded neurons had electrophysiological characteristics similar to those of regular-firing pyramidal cells and were in layers III to V, which was confirmed by intracellular staining with Lucifer yellow. Local extracellular stimulation evoked a sequence of excitatory and inhibitory postsynaptic potentials. After application of the gamma-aminobutyric acid antagonist, bicuculline (10-30 microM), extracellular stimulation induced large excitatory postsynaptic potentials and epileptiform bursts. Spontaneous bursts occasionally occurred in bicuculline. This effect of bicuculline was observed in all the tissue samples, even those from infant patients (n = 4, age 8-16 months). Kynurenic acid depressed or abolished both spontaneous and stimulation-induced bursts. The competitive antagonist for N-methyl-D-aspartate receptors, DL-2-amino-5-phosphonopentanoic acid decreased the duration of bicuculline-induced bursts. These data provide evidence that, similar to rat and cat neocortex, excitatory and inhibitory amino acids are important transmitters to pyramidal cells in immature human neocortex.

Patterns of tachykinin expression and localization in developing feline neostriatum.

The development of tachykinins in the neostriatum was determined qualitatively in order to characterize the ontogeny of an early-forming neostriatal peptidergic system. Tachykinins were detected by immunohistochemistry in fetal, postnatal, and adult cats. Neostriatal cells and neurites expressed tachykinins as early as fetal age 30 and increased in frequency progressively with age. Initial tachykinin expression occurred in neostriatal neurons during their postmitotic migration. In the head of the caudate nucleus, clusters of tachykinin-containing cells and fibers formed between fetal days 35 and 45, when the distribution of labeled neurons changed from a dispersed to an aggregated pattern. Between fetal days 45 and 50, tachykinin-rich neuronal clusters increased in frequency and were distributed throughout the rostral caudate nucleus. In contrast to neurons in clusters, neurons in the complementary neuropil expressed tachykinins largely postnatally. Postnatal morphological maturation of tachykinin-containing neurons paralleled the morphogenesis of medium spiny neostriatal cells. In addition, the caudate nucleus and putamen followed different spatiotemporal gradients of tachykinin expression. These results indicate that tachykinins are expressed in neostriatal neurons during the early ontogeny of the neostriatum and may function as trophic factors before synaptogenesis.

Caudate neurons respond to excitatory and inhibitory amino acids in early postnatal periods in the cat.

This study was designed to determine whether caudate neurons would respond to microphoretic application of glutamate and gamma-aminobutyric acid (GABA) in early postnatal periods in the cat. Extracellular recordings were performed in 175 neurons in developing kittens and 114 neurons in adult cats. At the earliest ages tested (1-10 days), caudate cells were excited by microphoretic application of glutamate and were inhibited by application of GABA. The results also indicated that caudate units have lower response thresholds to application of glutamate and GABA in early postnatal periods than in later periods. Since previous findings indicated that synaptically mediated inhibitory potentials develop during later postnatal periods in the cat, the present findings suggest that receptors for GABA may be capable of functioning before presynaptic endings make operational contacts.

Intracellular neurophysiological analysis reveals alterations in excitation in striatal neurons in aged rats.

Intracellular recordings were used to characterize the physiological changes underlying decreases in excitation observed in striatal neurons during the aging process. Rats were divided into 3 age groups: young (3-5 months), middle-aged (10-12 months) and aged (greater than 24 months). All experiments were performed in urethane-anesthetized rats. Recordings were obtained from 33 neurons in young, 17 in middle-aged and 20 in aged rats. When identified by intracellular injections of Lucifer yellow all recorded neurons were medium-sized spiny cells. Resting membrane potentials were at least -40 mV and action potentials greater than 35 mV. Postsynaptic responses were evoked by stimulation of frontal cortex. In all recorded neurons, regardless of age, excitatory postsynaptic potentials (EPSPs) could be evoked. However, the threshold currents for eliciting both EPSPs and synaptically driven action potentials were significantly higher in neurons obtained from aged rats than those recorded in the other two groups. Other changes in excitation in aged striatal neurons consisted of absence of spontaneously occurring EPSPs, higher current to induce firing by intracellular injections of depolarizing current and an inability of orthodromically induced action potentials to follow paired stimulation pulses to the cortex at short interpulse intervals. These data were interpreted to indicate that a combination of changes in synaptic connectivity and in membrane properties underlie the decreases in excitation. Together with our previous findings obtained from aged cats these results indicate that decreased neuronal excitability is a major effect of aging in the striatum.

Kynurenic acid antagonizes the excitatory postsynaptic potential elicited in neostriatal neurons in the in vitro slice of the rat.

Stimulation of corpus callosum in rat brain slices evoked an excitatory postsynaptic potential (EPSP) in neostriatal neurons. This EPSP is greatly reduced by exposing the slice to kynurenic acid (KY). The action of KY is reversed when the preparation is bathed in normal Ringer's solution. KY reduces the EPSP amplitude in a dose-dependent fashion, with 1 mM KY attenuating the potential by 86%. The effect is not due to a conductance change, since KY treatment does not alter the neuron's input resistance.

Dye-coupling in the neostriatum of the rat: I. Modulation by dopamine-depleting lesions.

Evidence from experiments performed in turtle and fish retina suggests that dopamine (DA) modulates the permeability of gap junctions. The present experiment was aimed at determining if DA has a similar role in the mammalian neostriatum. Adults rats received one of four treatments: unilateral electrolytic substantia nigra lesions, unilateral injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra, unilateral neocortical aspiration, or no treatment. After 3-5 weeks, neostriata from both sides of the brain were prepared for in vitro intracellular recordings. Recorded neurons (N approximately 150) were filled with Lucifer Yellow (LY), a low molecular weight dye that crosses gap junctions. In animals with electrolytic nigral lesions, dye-coupling in the ipsilateral neostriatum occurred after 38% of the intracellular injections. After 6-OHDA lesions, 19% of the injections produced dye-coupling in the ipsilateral neostriatum. This difference may have been accounted for by the fact that electrolytic lesions produced a greater degree of DA loss than 6-OHDA injections. Both of these percentages contrast with the very small percentage of dye-coupling found in intact animals or in animals with neocortical lesions. Dye-coupling occurred only between medium-sized spiny cells. No morphological differences between dye-coupled and non-dye-coupled cells were observed with light microscopy. Overall, passive and active electrophysiological properties of dye-coupled and single neurons were similar. The results suggest that DA may function in the neostriatum to control permeability of gap junctions.

Dye-coupling in the neostriatum of the rat: II. Decreased coupling between neurons during development.

Physiological and morphological evidence for coupling between neostriatal neurons was obtained from the developing rat. Intracellular injections of Lucifer Yellow-CH (LY) were made in rat neostriatal slices to study dye transfer (coupling) between neurons. The incidence of interneuronal coupling was 70% in early postnatal (P) periods and declined gradually to 10% in the adult. The number of neurons filled by a single intracellular injection also declined with age. LY injection into single neurons commonly marked aggregates of 4 to 6 cells in neonates. Single injections never produced more than one coupled pair in P20 or older rats. Neurons in which fast prepotentials (FPPs) could be evoked were consistently found to be dye-coupled. FPPs were resistant to collision with action potentials generated by intracellular current injection. When chemical synaptic transmission was blocked Mn2+, short-latency depolarizations (SLDs) could be evoked by extracellular stimulation. The SLDs were distinguished from chemical synaptic potentials by their "all or none" nature and by their insensitivity to changes in membrane potential. No SLDs were observed in adult neurons. FPPs and SLDs may be indicators of electronic transmission between coupled cells. The high incidence of coupling early in development might reflect intercellular communication that contributes to the differentiation and growth of neostriatal neurons.