Effects of endorphins on single myenteric neurons

Methionine-enkephalin, leucine-enkephalin and beta-endorphin were applied in known concentrations to an in vitro preparation of myenteric neurons from the guinea-pig ileum. All 3 substances caused a rapid, reversible and dose related inhibition of the firing of myenteric neurons induced and recorded with extracellular suction electrodes. This inhibition of firing occurred at low agonist concentrations (1-300 nM) and was reversed by naloxone and a benzomorphan narcotic antagonist. The inhibition persisted in solutions which were completely free of calcium ions -- thus indicating that the observed effect is taking place directly on the neuron from which the recording is made, and that calcium ions are not required for this inhibitory action of endorphins on neuronal firing.     

Inhibitory effect of cholecystokinin octapeptide on neurons in the nucleus tractus solitarius

We investigated the effect of the cholecystokinin octapeptide (CCK8) applied locally to neurons of the nucleus tractus solitarius (NTS). Results demonstrate an inhibitory effect of CCK8 on spike discharges including those related to respiration. It is suggested that CCK8 acts at this level through specific receptor mechanisms since CCK8-induced inhibitions were not reproduced by application of related peptides and were resistant to antagonists of different inhibitory transmitters.     

Human fetal cortical and striatal neural stem cells generate region-specific neurons in vitro and differentiate extensively to neurons after intrastriatal transplantation in neonatal rats

Human fetal brain is a potential source of neural stem cells (NSCs) for cell replacement therapy in neurodegenerative diseases. We explored whether NSCs isolated from cortex and striatum of human fetuses, aged 6-9 weeks post-conception, maintain their regional identity and differentiate into specific neuron types in culture and after intrastriatal transplantation in neonatal rats. We observed no differences between cortex- and striatum-derived NSCs expanded as neurospheres in proliferative capacity, growth rate, secondary sphere formation, and expression of neural markers. After 4 weeks of differentiation in vitro, cortical and striatal NSCs gave rise to similar numbers of GABAergic and VMAT2- and parvalbumin-containing neurons. However, whereas cortical NSCs produced higher number of glutamatergic and tyrosine hydroxylase- and calretinin-positive neurons, several-fold more neurons expressing the striatal projection neuron marker, DARPP-32, were observed in cultures of striatal NSCs. Human cortical and striatal NSCs survived and migrated equally well after transplantation. The two NSC types also generated similar numbers of mature NeuN-positive neurons, which were several-fold higher at 4 months as compared to at 1 month after grafting. At 4 months, the grafts contained cells with morphologic characteristics of neurons, astrocytes, and oligodendrocytes. Many of neurons were expressing parvalbumin. Our data show that NSCs derived from human fetal cortex and striatum exhibit region-specific differentiation in vitro, and survive, migrate, and form mature neurons to the same extent after intrastriatal transplantation in newborn rats.     

Transmitters and reticulospinal neurons

Glycine and GABA strongly depress the firing of reticulospinal neurons, glycine being more effective than GABA. The effects of strychnine and bicuculline methochloride on synaptic inhibition and on the actions of these amino acids are consistent with the earlier evidence that both glycine and GABA are inhibitory transmitters in the medullary reticular formation. However, although strychnine is consistently a relatively specific antagonist of glycine, bicuculline methochloride is far less specific in distinguishing between glycine and GABA on reticulospinal neurons. Studies of synaptic inhibition in the brain stem using bicuculline methochloride alone are therefore to be interpreted with caution. Both convulsants should be tested on the actions of glycine and GABA before conclusions about transmitter identity are made. Large propertions of reticulospinal neurons appear to be unaffected by ACh, 5-HT, NA, and DA. Of the amine-sensitive reticulospinal neurons, ACh and DA usually depress firing whereas 5-HT and NA usually cause excitation. These effects, however, are generally weak (especially excitation), and it is difficult to draw firm conclusions about the possible functional significance of these substances on reticulospinal neurons.     

Comparison of neural precursor cell fate in second trimester human brain and spinal cord

Neural transplantation holds promise for the treatment of traumatic brain and spinal cord injury by replacing lost cellular elements as well as repairing neural damage. Fetal human stem cells derived from central nervous system (CNS) tissue are potential transplantable sources for all cell types found in the mature human nervous system including neurons, astrocytes and oligodendroglia. Although nearly all areas of the fetal human neuraxis contain undifferentiated neural precursor cells, the phenotypic fate of the daughter cells might vary from one region to another during a specific developmental period. The purpose of this study was to compare the various cell types derived from neural precursors cultured from second trimester fetal human brain and spinal cord. To this end, brains (n = 8) and spinal cords (n = 8) of 15-24 week fetuses were dissociated and grown in culture medium supplemented with epidermal growth factor (EGF), basic fibroblast growth factor (FGF) and leukemia inhibitory factor (LIF). The proliferating precursor cells from both brain and spinal cord grew as spherical masses that were plated on laminin-coated dishes after seven days in culture. During the next 5-7 days, the cells that emerged from these spheres were fixed and processed for immunocytochemistry. Brain derived spheres gave rise to cells expressing antigens specific for neurons (MAP-2ab and neuron specific-intermediate filaments), astrocytes (GFAP) and oligodendrocytes (A007). In contrast, cells that emerged from spinal cord derived spheres were only immunoreactive for GFAP. These data suggest that neuroepithelial precursor cells from different CNS regions, although similar in their responsiveness to proliferative growth factors, might differ in their ability to generate different cell types in the adult CNS.     

ACh and ATP mediate excitatory transmission in cat carotid identified chemoreceptor units in vitro

Several molecules have been proposed as excitatory transmitters between glomus (type 1) cells and nerve terminals of petrosal ganglion (PG) neurons in the carotid body (CB). We tested whether ACh and ATP have a role to play as excitatory transmitters in the cat CB by recording intracellularly from identified PG neurons functionally connected to the CB in vitro. PG neurons projecting to the CB were classified according to their intracellular responses as: (a) neurons with humped action potentials (hAP neurons) responding phasically to long-lasting depolarizing pulses (53/67), and (b) neurons with smooth action potentials (non-hAP neurons) that fire tonically during long-lasting depolarizations (14/67). CB stimulation by stop flow and/or acidosis induced activity in 28 of 39 hAP-type neurons, being classified as chemosensory, but in none of the non-hAP neurons. Hexamethonium (10 microM) and suramin (100 microM) reversibly abolished the increased discharges evoked in chemosensory neurons (8/9) by stop flow or acidosis. Moreover, 24 of 27 chemosensory neurons responded to ganglionar application of ACh and ATP, while two neurons responded only to ACh and one to ATP. Mechanical deformation of the carotid sinus induced firing activity in 10 of 13 non-hAP neurons, but in none of the hAP neurons tested. Interestingly, 4/10 non-hAP neurons, which responded to carotid sinus mechanical stimulation also responded to ganglionar application of ATP, but were insensitive to ACh. Present results favor the hypothesis that ACh and ATP are excitatory transmitters in the cat CB, acting-at least-on the PG neuron terminals in the CB.     

家兔面神经核腹内侧区呼吸神经元的放电模式

通过细胞外记录的方法 ,探测成年家兔面神经核腹内侧区 ( vm NF)呼吸神经元的放电模式。实验采用健康成年家兔 46只 ,氨基甲酸乙酯麻醉 ,记录膈神经放电作为呼吸指标。在 vm NF内记录到 2 57个呼吸神经元单位放电 ,根据神经元放电模式及与膈神经放电的时相关系将记录到的呼吸神经元分为六类 :呼气递增神经元、前吸气神经元、吸气递增神经元、晚吸气神经元、后吸气神经元及吸 -呼跨时相神经元。其中呼气递增神经元和吸 -呼跨时相神经元占总数的 75.9%,这些神经元与 vm NF的“吸气切断”作用有密切关系。     

Co-localization and plasticity of transmitters in peripheral autonomic and sensory neurons

Immunohistochemical studies have shown that most peripheral autonomic and sensory ganglia are heterogeneous, consisting of several populations of neurons which can be distinguished by their content of peptide and non-peptide transmitters, and transmitter-associated enzymes. Many neurons contain several different potential transmitters, especially neuropeptides. Some neuropeptides have been localized in more than one population of autonomic and sensory neurons. However, the peptide often occurs together with a distinctive combination of additional transmitters in each neuronal class. The precise combination of transmitters found in any individual neuron is highly correlated with the peripheral target of the neuron. This indicates that immunohistochemically defined neuronal populations represent distinct functional classes of neurons. In an increasing number of cases, many of the potential transmitters contained in a particular neuron have been shown to be released from the nerve terminals, and to contribute to presynaptic or postsynaptic effects of nerve activation. Despite this association between the combination of potential transmitters contained in a neuron, and the function of the neuron, not all transmitters or transmitter-associated enzymes are expressed equally at all times in the life of a neuron: the levels of some substances change dramatically during development; some are detected only after experimental alteration of the environment of the developing or mature neurons. Taken together, these results indicate that, during development, pathway-specific information influences the differentiation of peripheral autonomic and sensory neurons. Furthermore, the expression of neuropeptides and transmitter-associated enzymes in a particular neuron appears to be under continuous regulation. These phenomena demonstrate the complexity and precision involved in development and maintenance of the peripheral autonomic and sensory nervous systems.     

Three types of reticular neurons involved in the spinobulbo-spinal reflex of cats

Reticular neuron activity was recorded in 28 chloralosed cats in order to analyze the reflex arc of the spino-bulbo-spinal (SBS) reflex. Three types of reticular neurons, types I (input), II (output) and III (relay), were identified by unit discharges in response to stimulation of the sural nerve.

(1) Type I (input) neurons received spinal ascending volleys monosynaptically and responded to stimulation of the sural nerve with spikes of low amplitude and short latency. Unit spikes, however, were not produced by stimulation of the superficial radial nerve and the sensorimotor cortex. These input neurons were located in the dorsocaudal part of the medial bulbar reticular formation.

(2) Type II (output) neurons were part of the reticulospinal tract, which sends axons to the spinal cord, since these neurons exhibited antidromic spikes following stimulation of the ventrolateral funiculus of the spinal cord. Unit spikes were evoked by stimulation either to the sural or superficial radial nerves. These neurons were located in the ventrocaudal part of the medial bulbar reticular formation.

(3) Type III neurons included relay neurons. Unit spikes were evoked by stimulation of the sural nerve, superficial radial nerve and sensorimotor cortex. However, unit discharges were not obtained by antidromic stimulation to the reticulospinal tract. These neurons were distributed widely in the brain stem, both in the bulb and pons.

(4) Latency difference of unit discharges between input and output neurons was 3.5–5 msec, indicating the presence of interneurons (relays) between input and output neurons. Spikes of output neurons with 3.8–4.2 msec latency were observed following stimulation of the region where input neuron activity was found. We may conclude that three kinds of reticular neurons, input, relay and output, were involved in pathways of the SBS reflex.

Transmitter sensitivities in oval neurons from rat brainstem cultures

Using cultures of dissociated neurons from the lower brainstem of 14-15-day-old rat embryos, we studied a specific relation between neuronal activities of small-sized oval neurons and their sensitivities to various transmitter substances. Oval neurons were characterized by non-effective responses to acetylcholine and a facilitatory response to both leucine- and methionine-enkephalin.     

Taste responses in the superior secondary gustatory nucleus of the carp, cyprinus carpio L.

Single unit discharges in the superior secondary gustatory nucleus of the carp, Cyprinus carpio L., were studied electrophysiologically in response to chemical stimulation of the external chemoreceptors of the facial skin surface.Of 36 gustatory neurons recorded, 80.6% were facilitated by taste stimuli and 19.4% were inhibited. The gustatory neurons were classified according to their responsiveness to the 4 basic taste substances and, except the inhibitory type, did not differ remarkably from the primary and secondary gustatory neurons. More inhibitory type (19.4%) neurons occurred at higher levels of the gustatory system. As in the primary and secondary levels, sodium chloride and acetic acid solutions were more effective stimuli than quinine HCl and sucrose.The ascending secondary gustatory fibers project bilaterally to the superior gustatory nucleus of the carp. About 20% of the gustatory neurons respond to stimulation of only the contralateral facial skin while 27.8% respond to stimulation of either side of the face. The latter neuron type showed very complicated responses, and were classified into ‘Uniform’, ‘Summation’, ‘Contra.Ipsi.’ and ‘Quality field’ types. The remaining 50% of the neurons respond only to stimulation on the ipsilateral side.     

Chemosensitivity of hypophysiotropic neurons to the microelectrophoresis of biogenic amines

The purpose of this study was to determine whether norepinephrine (NE), dopamine (DA), serotonin (5-HT), acetylcholine (ACh) and glutamate (Glut) when applied in the immediate vicinity and in minute quantities to single neurons within the preoptic-hypothalamic complex via microelectrophoresis, could modulate their electrical activity. The action of these putative neurotransmitters on medial-preoptic (MPO) and arcuate-ventromedial (ARC-VM) neurons was studied in the urethane anesthetized, ovariectomized female rat. Multi-barrelled glass microelectrodes were used for extracellular recording and for microelectrophoresis of the putative transmitters. Four specific neuron types were identified by median eminence electrical stimulation; namely, antidromically identified (AI) MPO neurons, uninvaded MPO neurons, AI ARC-VM neurons and uninvaded ARC-VM neurons. The major findings based on responsive neurons (i.e., those neurons which reacted to the chemical application by an increase or decrease in spontaneous activity) are summarized. The data demonstrate that NE had a pronounced excitatory effect on uninvaded and AI ARC-VM neurons and an inhibitory influence on AI MPO neurons. The influence of dopamine was not as clearly defined, although there was a slight trend towards excitation in uninvaded MPO neurons and inhibition in AI MPO neurons. Results based on the testing with 5-HT showed it to have an inhibitory action on uninvaded MPO neurons. Furthermore, ACh and Glut were shown to have an excitatory action on the majority of responsive neurons tested. The remaining neurons tested with either NE, DA or 5-HT displayed a similar number of excitatory and inhibitory responses. The findings obtained provide positive support for a catecholaminergic and cholinergic regulation or neurons projecting towards the median eminence which are presumably involved in pituitary function.     

Neuron-specific expression of therapeutic proteins: evaluation of different cellular promoters in recombinant adenoviral vectors

In order to achieve neuron-restricted expression of antiapoptotic proteins, cellular promoters were investigated for their expression profiles in the context of adenoviral vectors. Both the synapsin 1 gene and the tubulin alpha1 gene promoters were strictly neuron specific in cocultures of primary neurons with their essential feeder cells. The neuron-specific enolase gene promoter exhibited only weak activity in cultured hippocampal neurons and was not neuron specific in preparations of cerebellar granule cells. By attaining virtually 100% transduction efficiency we were able to generate "quasi-transgenic" primary neuron cultures using both differentiated and completely undifferentiated hippocampal neurons. In a functional assay, we used the synapsin promoter to evaluate the effect of Bcl-X(L) overexpression on potassium-withdrawal-induced apoptosis of cerebellar granule neurons. We found nearly complete inhibition of caspase-9 and -3 activation and apoptosis, indicating a major role for mitochondrial pathways in this paradigm of neuronal cell death. The excellent suitability of the synapsin promoter as a strong panneuronal promoter was further demonstrated by its restricted neuronal activity in various brain regions of adult rats in vivo.     

Innervation of hippocampal explants by central catecholaminergic neurons in co-cultured fetal mouse brain stem explants

The ability of central catecholaminergic neurons to grow into and establish functional connections with the hippocampus in vitro was studied using organotypic tissue culture. Brain stem explanted from the region of the locus coeruleus and hippocampal explants, from 18-day fetal mice, were maintained as co-cultures and were also grown separately. After 1-4 weeks these tissues were analyzed by glyoxylic acid-induced histofluorescence, by light and electron microscopic radioautography after incubation with [3H]norepinephrine, and by electrophysiology. Brain stem explants exhibited specifically fluorescent catecholaminergic cell bodies and varicose fibers after 2-4 weeks in culture. In contrast, no fluorescent cells or neurites could be seen in isolated hippocampal cultures grown for 2-3 weeks in vitro. When hippocampal explants were grown near brain stem explants, catecholaminergic fibers grew out of the brain stem and entered the hippocampus. In additional experiments, co-cultures of brain stem and hippocampus were incubated with [3H]norepinephrine (0.5 micron) and the monoamine oxidase inhibitor nialamide (100 micron). Radioautographic analyses revealed that brain stem neurites which entered the hippocampus took up norepinephrine, whereas neurites in the isolated hippocampal explants did not. Electron microscopic studies of the hippocampus showed varicose axon terminals within the hippocampus to be preferentially labeled. Although close relationships could be seen between labeled axons and dendrites, junctions exhibiting the membranous modifications associated with synapses were never seen. Electrophysiological studies suggested that the catecholaminergic neurites within the hippocampus were functional. Complex synaptically mediated slow wave discharges could be evoked by electrical stimuli in isolated hippocampal explants. Introduction of the beta adrenergic antagonist propranolol (0.4-4.3 micron) did not alter, or slightly depressed, these hippocampal discharges. On the other hand, in hippocampus-brain stem co-cultures, these concentrations of propranolol enhanced the complex hippocampal responses to brain stem or hippocampal stimuli. Similar enhancement of hippocampal responses by propranolol also occurred in these cocultures after acute surgical extirpation of the brain stem explant. The data suggest, therefore, that the action of propranol was probably to block adrenergic inhibitory connections with hippocampal synaptic networks. These experiments provide morphological and electrophysiological evidence that catecholaminergic neurons from fetal mouse brain stem maintained in organotypic tissue culture can grow into and functionally innervate the hippocampus.     

Inhibitory neuron‐specific Cre‐dependent red fluorescent labeling using VGAT BAC‐based transgenic mouse lines with identified transgene integration sites

Inhibitory neurons are crucial for shaping and regulating the dynamics of the entire network, and disturbances in these neurons contribute to brain disorders. Despite the recent progress in genetic labeling techniques, the heterogeneity of inhibitory neurons requires the development of highly characterized tools that allow accurate, convenient, and versatile visualization of inhibitory neurons in the mouse brain. Here, we report a novel genetic technique to visualize the vast majority and/or sparse subsets of inhibitory neurons in the mouse brain without using techniques that require advanced skills. We developed several lines of Cre‐dependent tdTomato reporter mice based on the vesicular GABA transporter (VGAT)‐BAC, named VGAT‐stop‐tdTomato mice. The most useful line (line #54) was selected for further analysis based on two characteristics: the inhibitory neuron‐specificity of tdTomato expression and the transgene integration site, which confers efficient breeding and fewer adverse effects resulting from transgene integration‐related genomic disruption. Robust and inhibitory neuron‐specific expression of tdTomato was observed in a wide range of developmental and cellular contexts. By breeding the VGAT‐stop‐tdTomato mouse (line #54) with a novel Cre driver mouse line, Galntl4‐CreER, sparse labeling of inhibitory neurons was achieved following tamoxifen administration. Furthermore, another interesting line (line #58) was generated through the unexpected integration of the transgene into the X‐chromosome and will be used to map X‐chromosome inactivation of inhibitory neurons. Taken together, our studies provide new, well‐characterized tools with which multiple aspects of inhibitory neurons can be studied in the mouse.     

Effects of intrathecal monoamine antagonists and naloxone on the descending inhibition of the spinal transmission of noxious input in rats: study with a new experimental model

An electrophysiological model has been developed to explore the transmitters and their relationships in the descending control of spinal transmission of noxious inputs. Nociceptive discharges were recorded extracellularly in parafascicular (Pf) neurons, and the caudal stump of longitudinally isolated dorsal half of the lower thoratic spinal cord was stimulated to simulate the descending volleys coming from the supraspinal structures. Nociceptive discharges in 34 Pf cells were markedly suppressed (83.2 ± 13.9%) by the preceding spinal stimulation. Phentolamine, methysergide and naloxone were separately administered with random sequence in each of 25 cells by an intrathecal route to observe if the descending inhibition could be blocked by these drugs. The results suggested that in the dorsal spinal cord there exist at least two neurochemically different descending inhibitory fiber systems which comprise either the long descending adrenergic or serotonergic fibers and, most of the adrenergic fibers are succeeded by a propriospinal opioidergic neuron while a few of the serotonergic fibers have such a succession.     

Differential action of amitriptyline on neurons in the trigeminal nucleus.

We studied the effect of amitriptyline (AMI) on neurons in the spinal trigeminal nucleus caudalis in cats anesthetized with alpha-chloralose. The IV injection of 1.0 to 4.0 mg/kg AMI had a differential effect on the inhibitory mechanisms controlling the responses of these neurons. AMI significantly enhanced the segmental inhibition (SI) of wide dynamic range (WDR) neurons but had little or no effect on low-threshold mechanoceptive neurons. AMI also facilitated the SI of some nociceptive specific (NS) neurons and the periventricular inhibition of some WDR and NS neurons, but these effects were not statistically significant. Our observations suggest that AMI exerts its antineuralgic effect by enhancing the ability of SI to prevent excessive firing of WDR neurons. This supports the notion that neuropathic pain is caused by dysfunction of inhibitory mechanisms in the CNS.     

A comparative analysis of coordinated neuronal activity in the thalamic ventrobasal complex of rats and cats

There are substantial differences in the incidence of inhibitory neurons in the ventrobasal complex of rat and cat thalamus. This marked dissimilarity in neuronal composition suggests that there should be corresponding differences in the orchestration of neural activity in these regions during cutaneous stimulation. To explore this possibility, we conducted a cross-correlation analysis of neuronal activity in the ventroposterolateral (VPL) nucleus of anesthetized rats and cats. Pairs of neurons representing hairy skin were recorded simultaneously with one or two electrodes during air jet stimulation of multiple sites throughout the receptive fields. Cross-correlation histograms indicated that correlated activity among adjacent neurons occurred in three distinct patterns. In one pattern, classified as narrow-unimodal, the discharge of one neuron preceded a discharge in the partner neuron over a narrow interval of time (<5 ms). Narrow-bimodal patterns were characterized by responses in which the temporal order of discharges from the two neurons was variable, but the interspike intervals were always <5 ms. In wide-unimodal patterns, the discharge of one neuron was correlated with subsequent discharges in the partner neuron over a wide interval of time (>5 ms). In rat VPL, two-thirds of the 58 neuron pairs showing correlated responses were characterized by narrow-unimodal responses and nearly one-third of the neuron pairs displayed narrow-bimodal patterns. Only one pair of rat VPL neurons were characterized by a wide-unimodal pattern of coordination. By comparison, half of the 61 adjacent neuron pairs with coordinated responses in cat VPL were characterized by narrow-unimodal patterns. Slightly more than one-third of the correlated neuron pairs had narrow-bimodal patterns, while the remainder (13%) were classified as wide-unimodal responses. Pairs of neurons separated by 340–405 μm discharged synchronously in a pattern that was similar to the temporal relationship expressed in the narrow-bimodal patterns found among adjacent neurons. In both species, the wide-unimodal patterns had the strongest coordinated responses as measured by the correlation coefficient. Although inhibitory relationships did not appear in correlation histograms that had been correlated for stimulus coordination, cross-correlation analysis of the raw spike trains revealed brief (10–40 ms) periods of inhibition that were associated with cat VPL neurons exhibiting wide-unimodal coordination patterns. In rat VPL, most inhibition involved longer (30–60 ms) periods of inhibitory oscillations appearing amidst a much larger rhythmic pattern. These results suggest that correlation patterns transpiring over narrow (<5 ms) time intervals represent the coordination of activity among neighboring thalamocortical relay neurons. By contrast, wide-unimodal patterns appear to represent coordinated activity between a thalamocortical relay cell and an intrinsic inhibitory neuron.     

Analysis of clinical and electrophysiological findings in Jakob-Creutzfeldt disease

Summary Serial EEG and EMG investigations were performed in the course of a histologically verified case of Jakob-Creutzfeldt disease. Some electrophysiologic data, including visual-evoked responses were analyzed using a computer. Correlations between clinical and EEG findings suggest that the generator of the periodic discharges may be localized in some circumscribed area of the upper brain stem, probably the thalamus. The inhibitory effect of various narcotics suggests that the pacemaker of the triphasic discharges has relations to the nonspecific activating system.     

Kindling does not cause persistent changes in firing rates or transmitter sensitivities of substantia nigra pars reticulata neurons

These studies were undertaken to determine whether the kindling process induces persistent alterations in the functional status of neurons of the substantia nigra pars reticulata, a brain area identified previously as a site important in regulating the expression of generalized motor seizures. Extracellular, single-unit recordings of pars reticulata neurons were made in chloral hydrate-anesthetized, fully kindled rats (2–3 weeks after the last seizure), or unkindled control rats of the same age and weight. Kindling caused no alterations in several electrophysiological parameters examined. For instance, neither the number of active pars reticulata cells encountered, nor their firing rates, were significantly different between kindled and control groups. In addition, kindling failed to alter the sensitivities of pars reticulata neurons to iontophoretic application of two inhibitory transmitters, γ-aminobutyric acid and glycine, and two transmitters that excite these cells, glutamate and acetylcholine. These results suggest that while kindling produces enduring increases in seizure susceptibility, it causes no persistent interictal changes in either basal activity or several measures of transmitter sensitivity of substantia nigra pars reticulata neurons.