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PubMed2005

Functional mu opioid receptors are expressed in cholinergic interneurons of the rat dorsal striatum: territorial specificity and diurnal variation.

Striatal cholinergic interneurons play a crucial role in the control of movement as well as in motivational and learning aspects of behaviour. Neuropeptides regulate striatal cholinergic transmission and particularly activation of mu opioid receptor (MOR) inhibits acetylcholine (ACh) release in the dorsal striatum. In the present study we investigated whether this cholinergic transmission could be modulated by an enkephalin/MOR direct process. We show that mRNA and protein of MORs are expressed by cholinergic interneurons in the limbic/prefrontal territory but not by those in the sensorimotor territory of the dorsal striatum. These MORs are functional because potassium-evoked release of ACh from striatal synaptosomes was dose-dependently reduced by a selective MOR agonist, this effect being suppressed by a MOR antagonist. The MOR regulation of cholinergic interneurons presented a diurnal variation. (i) The percentage of cholinergic interneurons containing MORs that was 32% at the beginning of the light period (morning) increased to 80% in the afternoon. (ii) The MOR-mediated inhibition of synaptosomal ACh release was higher in the afternoon than in the morning. (iii) While preproenkephalin mRNA levels remained stable, enkephalin tissue content was the lowest (-32%) in the afternoon when the spontaneous (+35%) and the N-methyl-d-aspartate-evoked (+140%) releases of enkephalin (from microsuperfused slices) were the highest. Therefore, by acting on MORs present on cholinergic interneurons, endogenously released enkephalin reduces ACh release. This direct enkephalin/MOR regulation of cholinergic transmission that operates only in the limbic/prefrontal territory of the dorsal striatum might contribute to information processing in fronto-cortico-basal ganglia circuits.

Acetylcholine↗
PubMed2001

Unitary synaptic currents between lacunosum-moleculare interneurones and pyramidal cells in rat hippocampus.

1. Unitary inhibitory postsynaptic currents (uIPSCs) were characterised between 23 synaptically coupled interneurones at the border of stratum radiatum and lacunosum-moleculare (LM) and CA1 pyramidal cells (PYR) using dual whole-cell recordings and morphological identification in rat hippocampal slices. 2. LM interneurones presented a morphology typical of stellate cells, with a fusiform soma as well as dendritic and axonal arborisations in stratum radiatum and lacunosum-moleculare. 3. Single spikes in interneurones triggered uIPSCs in pyramidal cells that were blocked by the GABA(A) antagonist bicuculline and mediated by a chloride conductance. The latency, rise time, duration and decay time constant of uIPSCs were a function of amplitude in all pairs, suggesting a homogeneity in the population sampled. 4. During paired pulse stimulation, individual LM-PYR connections exhibited facilitation or depression. The paired pulse ratio was inversely related to the amplitude of the first response. The transition from facilitation to depression occurred at 26 % of the maximal amplitude of the first uIPSC. Paired pulse depression was not modified by CGP 55845 and thus was GABA(B) receptor independent. 5. CGP 55845 failed to modify the amplitude of uIPSCs, suggesting an absence of tonic presynaptic GABA(B) inhibition at LM-PYR connections. 6. Increasing GABA release by repetitive activation of interneurones failed to induce GABA(B) IPSCs. With extracellular minimal stimulation, increasing stimulation intensity above threshold, or repetitive activation, evoked GABA(B) IPSCs, probably as a result of coactivation of several GABAergic fibres. 7. Thus, dendritic inhibition by LM interneurones involves GABA(A) uIPSCs with kinetics dependent on response amplitude and subject to GABA(B)-independent paired pulse plasticity.

Animals↗
PubMed1972

An electrophysiological demonstration of the axonal projections of single spinal interneurones in the cat.

1. Single interneurones excited from group Ia afferents and located in the ventral horn of the spinal cord in the cat were activated antidromically by stimulation of their axons with one micro-electrode while recording extracellularly close to their somas with a second micro-electrode. The interneurones studied were those which, according to previous indirect evidence, should mediate the reciprocal Ia inhibition of motoneurones.2. Two subgroups of these interneurones were studied: those excited from group Ia afferents in the quadriceps (Q) and posterior bicepssemitendinosus (PBSt) nerves. Most of them could be activated from a number of separate loci in the PBSt and Q motor nuclei respectively and from the ventral or lateral funiculi.3. The location of the axonal branches and the extent of their branching in the motor nuclei were reconstructed by comparing the latencies of the responses and the thresholds (0.1-5 muA) for antidromic activation of single interneurones from different electrode positions in a number of tracks, having previously established the relation between the threshold and the distance from the stimulated fibres. For the main branches in the white matter the conduction velocity was found to be about 70 m/sec.4. The axonal projections of the investigated interneurones were found to be fully consistent with the hypothesis that they mediate reciprocal inhibition of motoneurones.

Action Potentials↗
PubMed1982

Two group of spinal interneurones that respond to stimulation of the abdominal viscera of the cat.

1. Recordings have been made from sixty-three spinal interneurones that received inputs from the abdominal viscera. These were divided into two groups: group A were sacral interneurones without either significant ascending projections or afferent input from the lumbar splanchnic nerves and group B were neurones with short ascending axons and afferent inputs from the lumbar splanchnic nerves, and often also from the pelvic and pudendal nerves.2. Somato-visceral convergence was common in both groups, and the somatic receptive fields of group A interneurones were in muscle and joints and less commonly skin innervated by sacral segments, whereas those of group B were innervated by lumbar and sacral segments.3. Within both groups of neurones there was a proportion that showed no response to distension or contractions of the viscera, (despite the fact that they responded to visceral nerve stimulation), and those which did respond showed graded changes in discharge rate as intravesical pressure was raised. Some cells received inputs from only one viscus: the receptive fields of these cells are described as simple and the effect of raising the pressure in that viscus was either to excite or to inhibit the central neurone. Other cells received convergent inputs from two viscera: their receptive fields are described as compound and the effect of raising intraluminal pressures in the viscera allowed a further subdivision of these cells into two types. Type I cells were either excited or inhibited by distension or contractions of either viscus. Type II cells were excited by natural stimulation of one of the innervated viscera but inhibited by similar changes in the other. The static pressure thresholds of these cells were 9+/-5 mmHg intravesical pressure, and 24+/-11 mmHg intracolonic pressure (means+/-s.d.).4. It is proposed that within the population of neurones described there are cells (group A interneurones) that either mediate the vesico- and colono-sphincteric reflexes or the colono-vesical interactions that can be seen in the micturition reflex pathway.5. It is proposed that the group B interneurones with short ascending projections mediate the vesico- and colono-sympathetic reflexes because their patterns of convergence, position in the spinal cord, latencies, and static pressure thresholds are consistent with those reflexes.

Abdomen↗
PubMed1991

The influence of contralateral primary afferents on Ia inhibitory interneurones in humans.

1. Contralateral influences on short latency reciprocal inhibition between wrist extensor and flexor muscles were investigated in twenty-two healthy volunteers. Reciprocal inhibition, probably mediated through the Ia inhibitory interneurone, was measured by conditioning the flexor carpi radialis (FCR) H reflex by weak stimulation of the ipsilateral radial nerve. Maximum reciprocal inhibition occurring at a precise delay between conditioning and conditioned stimulations was taken as the test level of inhibition. 2. Contralateral median or radial nerves were stimulated at short intervals before the onset of reciprocal inhibition. The latter was increased by 8.6% after median nerve stimulation and decreased by 16.5% after radial nerve stimulation. 3. The contribution of sensory fibres in the two nerves to contralateral effects was investigated by stimulating purely sensory branches of the nerves. No clear modification of the contralateral reciprocal inhibition was observed. The effects produced by mixed nerve stimulation are thus likely to have been mediated by Ia fibres. 4. In three hemiplegic patients where reciprocal inhibition was reduced unilaterally, stimulation on the spastic side produced contralateral effects similar to those observed in normal subjects. This result indicates that contralateral effects are not mediated through the Ia inhibitory interneurone ipsilateral to the conditioning stimulus. 5. Since contralateral effects occur after short delays (2 ms, median nerve; 3 ms, radial nerve), we suggest a functional scheme in which the excitability of Ia inhibitory interneurones is modified by contralateral primary afferents via the interneurones activated by group I fibres, probably Ia fibres. The short delays indicate that the interneurone transmitting primary afferent influences to the contralateral side is probably excitatory.

Adolescent↗
PubMed2002

Serotonin 5-HT(3) receptors in rat CA1 hippocampal interneurons: functional and molecular characterization.

The molecular makeup of the serotonin 5-HT(3) receptor (5-HT(3)R) channel was investigated in rat hippocampal CA1 interneurons in slices using single-cell RT-PCR and patch-clamp recording techniques. We tested for the expression of the 5-HT(3A) (both short and long splice variants) and 5-HT(3B) subunits, as well as the expression of the alpha4 subunit of the neuronal nicotinic ACh receptors (nAChRs), the latter of which has been shown to co-assemble with the 5-HT(3A) subunit in heterologous expression systems. Both the 5-HT(3A)-short and alpha4-nAChR subunits were expressed in these interneurons, but we could not detect any expression of either the 5-HT(3B) or the 5-HT(3A)-long subunits. Furthermore, there was a strong tendency for the 5-HT(3A)-short and alpha4-nAChR subunits to be co-expressed in individual interneurons. To assess whether there was any functional evidence for co-assembly between the 5-HT(3A)-short and alpha4-nAChR subunits, we used the sulphydryl agent 2-aminoethyl methanethiosulphonate (MTSEA), which has previously been shown to modulate expressed 5-HT(3)Rs that contain the alpha4-nAChR subunit. In half of the interneurons examined, MTSEA significantly enhanced the amplitude of the 5-HT(3)R-mediated responses, which is consistent with the notion that the alpha4-nAChR subunit co-assembles with the 5-HT(3A) subunit to form a native heteromeric 5-HT(3)R channel in rat CA1 hippocampal interneurons in vivo. In addition, the single-channel properties of the 5-HT(3)R were investigated in outside-out patches. No resolvable single-channel currents were observed. Using non-stationary fluctuation analysis, we obtained an estimate of the single-channel conductance of 4 pS, which is well below that expected for channels containing both the 5-HT(3A) and 5-HT(3B) subunits.

Action Potentials↗
PubMed2003

Modulation of inhibitory autapses and synapses on rat CA1 interneurones by GABA(A) receptor ligands.

To determine whether autaptic inhibition plays a functional role in the adult hippocampus, the action potential afterhyperpolarisations (spike AHPs) of CA1 interneurones were investigated in 25 basket, three bistratified and eight axo-axonic cells. The spike AHPs showed two minima in all regular-spiking (5), burst-firing (3) and in many fast-spiking cells (17:28). The fast component had a time-to-peak (TTP) of 1.2 +/- 0.5 ms, the slower TTP was very variable (range of 3.3-103 ms). The AHP width at half-amplitude (HW) was 12.5 +/- 5.7 ms in fast-spiking, 29.3 +/- 18 ms in regular-spiking and 99.7 +/- 42 ms in burst-firing cells. Axo-axonic cells never establish autapses, and the fast-spiking variety showed narrow (HW: 3.9 +/- 0.7 ms) spike AHPs with only one AHP minimum (TTP: 0.9 +/- 0.1 ms). When challenged with GABA(A) receptor modulators, spike AHPs in basket and bistratified cells were enhanced by zolpidem (HW by 18.4 +/- 6.2 % in 10:15 cells tested), diazepam (45.2 +/- 0.5 %, 6:7), etomidate (43.9 +/- 36 %, 6:8) and pentobarbitone sodium (41 %, 1:1), and were depressed by bicuculline (-41 +/- 5.7 %, 5:8) and picrotoxin (-54 %, 1:1), and the enhancement produced by zolpidem was reduced by flumazenil (-31 +/- 13 %, relative to the AHP HW during exposure to zolpidem, 3:4). Neuronal excitability was modulated in parallel. The spike AHPs of three axo-axonic cells tested showed no sensitivity to etomidate, pentobarbitone or diazepam. Interneurone-to-interneurone inhibitory postsynaptic potentials (IPSPs), studied with dual intracellular recordings, had time courses resembling those of the spike AHPs. The IPSP HW was 13.4 +/- 2.8 ms in fast-spiking (n = 16) and 28.7 +/- 5.8 ms in regular-spiking/burst-firing cells (n = 6), and the benzodiazepine1-selective modulator zolpidem strongly enhanced these IPSPs (45 +/- 28 %, n = 5). Interneurones with spike AHPs affected by the GABA(A) receptor ligands exhibited 3.8 +/- 1.9 close autaptic appositions. In three basket cells studied at the ultrastructural level 6 of 6, 1 of 2 and 1 of 2 close appositions were confirmed as autapses. Therefore, in the hippocampus autaptic connections contribute to spike AHPs in many interneurones. These autapses influence neuronal firing and responses to GABA(A) receptor ligands.

Action Potentials↗
PubMed2004

Synaptic interactions between pyramidal cells and interneurone subtypes during seizure-like activity in the rat hippocampus.

We have recently reported that excitatory GABAergic and glutamatergic mechanisms may be involved in the generation of seizure-like (ictal) rhythmic synchronization (afterdischarge), induced by a strong synaptic stimulation of the CA1 pyramidal cells in the mature rat hippocampus in vitro. To clarify the network mechanism of this neuronal synchronization, dual whole-cell patch-clamp recordings of the afterdischarge responses were performed simultaneously from a variety of interneurones and their neighbouring pyramidal cells in hippocampal CA1-isolated slice preparations. According to morphological and electrophysiological criteria, the recorded interneurones were then classified into distinct subtypes. The non-fast-spiking interneurones located in the strata lacunosum-moleculare and radiatum hardly discharged during the afterdischarge, whereas most of the fast-spiking and non-fast-spiking interneurones in the strata oriens and pyramidale, including the basket, chandelier and bistratified cells, exhibited prominent firings that were precisely synchronous with oscillatory responses in the pyramidal cells. Field potential recordings showed that excitatory synaptic transmissions might take place primarily in the strata oriens and pyramidale during the afterdischarge. Restricted lesions in the strata oriens and pyramidale, but not in the other layers, resulted in the complete desynchronization of afterdischarge activity, and also, local application of glutamate receptor antagonists to these layers blocked the expression of afterdischarge. The present findings indicate that the neuronal synchronization of epileptic afterdischarge may be accomplished in a 'positive feedback circuit' formed by the excitatory GABAergic interneurones and the glutamatergic pyramidal cells within the strata oriens and/or pyramidale of the hippocampal CA1 region.

2-Amino-5-phosphonovalerate↗
PubMed2004

Electrotonic coupling between stratum oriens interneurones in the intact in vitro mouse juvenile hippocampus.

Using the isolated juvenile (7-14 days) mouse whole hippocampus preparation, which contains intact complex local circuitry, 145 dual whole cell recordings were made from stratum oriens (s.o.) interneurones under infrared microscopy. In 11.7% of paired recordings, evidence for direct electrotonic coupling between the s.o. interneurones was obtained from the response of one interneurone to a long (400-600 ms) constant current pulse passed into the coupled interneurone. When specifically orienting the dual recordings in the transectional plane of the hippocampus, 18.5% of paired recordings showed electrotonic coupling. The coupling coefficient, estimated from averaged data, was 6.9 +/- 4.7%, ranging from 1.3 to 17.6%. The time constant of the electrotonically transmitted hyperpolarization was inversely related to the coupling coefficient between the two neurones. The electrotonic responses of one neurone to constant current pulses injected into the other coupled neurone were intermittent. Spikes in one of the coupled neurones were associated with small electrotonic EPSPs (spikelets) in the other coupled neurone, in those neuronal pairs with coupling coefficients greater than 10%. Failure of spikelet production following a spike in the coupled cell occurred 5-10% of the time. Electrotonic coupling and spikelets persisted in the presence of chemical synaptic transmission blockade by CNQX, APV and bicuculline, or in zero Ca(2+) perfusate, but were abolished by carbenoxolone (100 microm), a gap junctional blocker. These data confirm the existence of electrotonic coupling between s.o. interneurones, presumably via gap junctions located in dendrites.

Action Potentials↗
PubMed2004

Differential involvement of oriens/pyramidale interneurones in hippocampal network oscillations in vitro.

Using whole-cell patch-clamp recordings in conjunction with post hoc anatomy we investigated the physiological properties of hippocampal stratum oriens and stratum pyramidale inhibitory interneurones, before and following the induction of pharmacologically evoked gamma frequency network oscillations. Prior to kainate-induced transient epochs of gamma activity, two distinct classes of oriens interneurones, oriens lacunosum-moleculare (O-LM) and trilaminar cells, showed prominent differences in their membrane and firing properties, as well as in the amplitude and kinetics of their excitatory postsynaptic events. In the active network both types of neurone received a phasic barrage of gamma frequency excitatory inputs but, due to their differential functional integration, showed clear differences in their output patterns. While O-LM cells fired intermittently at theta frequency, trilaminar interneurones discharged on every gamma cycle and showed a propensity to fire spike doublets. Two other classes of fast spiking interneurones, perisomatic targeting basket and bistratified cells, in the active network discharged predominantly single action potentials on every gamma cycle. Thus, within a locally excited network, O-LM cells are likely to provide a theta-frequency patterned output to distal dendritic segments, whereas basket and bistratified cells are involved in the generation of locally synchronous gamma band oscillations. The anatomy and output profile of trilaminar cells suggest they are involved in the projection of locally generated gamma rhythms to distal sites. Therefore a division of labour appears to exist whereby different frequencies and spatiotemporal properties of hippocampal rhythms are mediated by different interneurone subtypes.

Animals↗
PubMed2004

Defined types of cortical interneurone structure space and spike timing in the hippocampus.

The cerebral cortex encodes, stores and combines information about the internal and external environment in rhythmic activity of multiple frequency ranges. Neurones of the cortex can be defined, recognized and compared on the comprehensive application of the following measures: (i) brain area- and cell domain-specific distribution of input and output synapses, (ii) expression of molecules involved in cell signalling, (iii) membrane and synaptic properties reflecting the expression of membrane proteins, (iv) temporal structure of firing in vivo, resulting from (i)-(iii). Spatial and temporal measures of neurones in the network reflect an indivisible unity of evolutionary design, i.e. neurones do not have separate structure or function. The blueprint of this design is most easily accessible in the CA1 area of the hippocampus, where a relatively uniform population of pyramidal cells and their inputs follow an instantly recognizable laminated pattern and act within stereotyped network activity patterns. Reviewing the cell types and their spatio-temporal interactions, we suggest that CA1 pyramidal cells are supported by at least 16 distinct types of GABAergic neurone. During a given behaviour-contingent network oscillation, interneurones of a given type exhibit similar firing patterns. During different network oscillations representing two distinct brain states, interneurones of the same class show different firing patterns modulating their postsynaptic target-domain in a brain-state-dependent manner. These results suggest roles for specific interneurone types in structuring the activity of pyramidal cells via their respective target domains, and accurately timing and synchronizing pyramidal cell discharge, rather than providing generalized inhibition. Finally, interneurones belonging to different classes may fire preferentially at distinct time points during a given oscillation. As different interneurones innervate distinct domains of the pyramidal cells, the different compartments will receive GABAergic input differentiated in time. Such a dynamic, spatio-temporal, GABAergic control, which evolves distinct patterns during different brain states, is ideally suited to regulating the input integration of individual pyramidal cells contributing to the formation of cell assemblies and representations in the hippocampus and, probably, throughout the cerebral cortex.

Animals↗
PubMed1971

Bilateral symmetry and interneuronal organization in the buccal ganglia of Aplysia.

Principles of functional organization of the bilaterally symmetric buccal ganglia of Aplysia were studied in 20 identified cells used as a reference population. Four of the identified cells (two in each ganglion) are multiaction interneurons, each of which innervates six identified ipsilateral follower cells, mediating cholinergic excitation to one cell and cholinergic inhibition to five others. Bilateral coordination is effected by common inputs to all four interneurons. Ipsilateral pairs of interneurons are electrotonically coupled and produce identical synaptic actions on their common follower population. This apparent redundancy of interneuronal action leads to feed-forward summation, eliciting amplified synaptic output from each interneuron pair.

Animals↗
PubMed2000

Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex.

A puzzling feature of the neocortex is the rich array of inhibitory interneurons. Multiple neuron recordings revealed numerous electrophysiological-anatomical subclasses of neocortical gamma-aminobutyric acid-ergic (GABAergic) interneurons and three types of GABAergic synapses. The type of synapse used by each interneuron to influence its neighbors follows three functional organizing principles. These principles suggest that inhibitory synapses could shape the impact of different interneurons according to their specific spatiotemporal patterns of activity and that GABAergic interneuron and synapse diversity may enable combinatorial inhibitory effects in the neocortex.

Action Potentials↗
PubMed1993

Identification of baroreceptor reflex interneurons in the caudal ventrolateral medulla.

Interrupting neuronal activity in the caudal ventrolateral medulla (CVL) abolishes baroreceptor-mediated sympathoinhibition and vasodepressor responses. In the present study we identified CVL neurons that function as interneurons in the baroreceptor reflex arc. The mean antidromic onset latency of CVL neurons (5 ms) after stimulation in the rostral ventrolateral medulla (RVL) suggests that they transmit information to the RVL via unmyelinated axons. Stimulation of baroreceptor afferents in the aortic depressor nerve (ADN) excited CVL neurons projecting to the RVL with onset latencies between 15 and 45 ms. The short-latency ADN stimulus-evoked excitation of CVL barosensory interneurons preceded the onset of the ADN stimulus-evoked inhibition of RVL-spinal sympathoexcitatory neurons. Longer-latency ADN-evoked CVL neuronal responses may arise from activation of unmyelinated ADN afferents that can prolong the inhibition of RVL sympathoexcitatory neurons. The excitation of CVL barosensory interneurons resulting from the systolic pressure rise was followed by a period of decreased excitability of RVL sympatho-excitatory neurons, which was of comparable duration to the increase in the discharge probability of CVL neurons. Our characterization of baroreceptor reflex interneurons in the CVL suggests that transmission of baroreceptor information involves a complex activation of medullary interneurons responding selectively to different aspects of the arterial pressure stimulus.

Animals↗
PubMed2004

Statocyst hair cell activation of identified interneurons and foot contraction motor neurons in Hermissenda.

Pavlovian conditioning of Hermissenda produces both light-elicited inhibition of normal positive phototactic behavior and conditioned stimulus (CS)-elicited foot-shortening. Rotation, the unconditioned stimulus (US) elicits foot-shortening and reduced forward ciliary locomotion. The neural circuit supporting ciliary locomotion and its modulation by light is known in some detail. However, the neural circuits responsible for rotation-elicited foot-shortening and reduced forward ciliary locomotion are not known. Here we describe components of the neural circuit in Hermissenda that produce anterior foot contraction and ciliary activation mediated by statocyst hair cells. We have characterized in semi-intact preparations newly identified pedal ventral contraction motor neurons (VCMNs) and interneurons (I(b)). Type I(b) interneurons receive polysynaptic input from statocyst hair cells and project directly to VCMNs and cilia-activating motor neurons. Depolarization of VCMNs with extrinsic current in normal artificial seawater (ASW) and high-divalent cation ASW, and under conditions where central synaptic transmission was suppressed with 5 mM Ni(2+) ASW, elicited a contraction of the ipsilateral anterior foot measured from videotape recordings. Mechanical displacement of the statocyst or depolarization of identified statocyst hair cells with extrinsic current elicited spikes and complex excitatory postsynaptic potentials (EPSPs) in type I(b) interneurons and complex EPSPs and spikes recorded in VCMNs. Type I(b) interneurons are electrically coupled and project to VCMNs and VP1 cilia-activating motor neurons located in the contralateral pedal ganglia. The results indicate that statocyst hair-cell-mediated anterior foot contraction and graviceptive ciliary locomotion involve different interneuronal circuit components from the circuit previously identified as supporting light modulated ciliary locomotion.

Action Potentials↗
PubMed2006

Intrinsic properties shape the firing pattern of ventral horn interneurons from the spinal cord of the adult turtle.

Interneurons in the ventral horn of the spinal cord play a central role in motor control. In adult vertebrates, their intrinsic properties are poorly described because of the lack of in vitro preparations from the spinal cord of mature mammals. Taking advantage of the high resistance to anoxia in the adult turtle, we used a slice preparation from the spinal cord. We used the whole cell blind patch-clamp technique to record from ventral horn interneurons. We characterized their firing patterns in response to depolarizing current pulses and found that all the interneurons fired repetitively. They displayed bursting, adapting, delayed, accelerating, or oscillating firing patterns. By combining electrophysiological and pharmacological tests, we showed that interneurons expressed slow inward rectification, plateau potential, voltage-sensitive transient outward rectification, and low-threshold spikes. These results demonstrate a diversity of intrinsic properties that may enable a rich repertoire of activity patterns in the network of ventral horn interneurons.

Action Potentials↗
PubMed2002

Dopamine excites fast-spiking interneurons in the striatum.

The striatum is the main recipient of dopaminergic innervation. Striatal projection neurons are controlled by cholinergic and GABAergic interneurons. The effects of dopamine on projection neurons and cholinergic interneurons have been described. Its action on GABAergic interneurons, however, is still unknown. We studied the effects of dopamine on fast-spiking (FS) GABAergic interneurons in vitro, with intracellular recordings. Bath application of dopamine elicited a depolarization accompanied by an increase in membrane input resistance (an effect that persisted in the presence of tetrodotoxin) and action-potential discharge. These effects were mimicked by the D1-like dopamine receptor agonist SKF38393 but not by the D2-like agonist quinpirole. Evoked corticostriatal glutamatergic synaptic currents were not affected by dopamine. Conversely, GABAergic currents evoked by intrastriatal stimulation were reversibly depressed by dopamine and D2-like, but not D1-like, agonists. Cocaine elicited effects similar to those of dopamine on membrane potential and synaptic currents. These results show that endogenous dopamine exerts a dual excitatory action on FS interneurons, by directly depolarizing them (through D1-like receptors) and by reducing their synaptic inhibition (through presynaptic D2-like receptors).

Action Potentials↗
PubMed2006

Striatal cholinergic interneurons express a receptor-insensitive homomeric TASK-3-like background K+ current.

Large aspiny cholinergic interneurons provide the sole source of striatal acetylcholine, a neurotransmitter essential for normal basal ganglia function. Cholinergic interneurons engage in multiple firing patterns that depend on interactions among various voltage-dependent ion channels active at different membrane potentials. Leak conductances, particularly leak K(+) channels, are of primary importance in establishing the prevailing membrane potential. We have combined molecular neuroanatomy with whole cell electrophysiology to demonstrate that TASK-3 (K(2P)9.1, Kcnk9) subunits contribute to leak K(+) currents in striatal cholinergic interneurons. Immunostaining for choline acetyltransferase was combined with TASK-3 labeling, using nonradioactive cRNA probes or antisera selective for TASK-3, to demonstrate that striatal cholinergic neurons universally express TASK-3. Consistent with this, we isolated a pH-, anesthetic-, and Zn(2+)-sensitive current with properties expected of TASK-3 homodimeric channels. Surprisingly, activation of Galphaq-linked receptors (metabotropic glutamate mGluR1/5 or histamine H1) did not appear to modulate native interneuron TASK-3-like currents. Together, our data indicate that homomeric TASK-3-like background K(+) currents contribute to establishing membrane potential in striatal cholinergic interneurons and they suggest that receptor modulation of TASK channels is dependent on cell context.

Animals↗