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PubMed2004

Development of an inhibitory interneuronal circuit in the embryonic spinal cord.

Locally projecting inhibitory interneurons play a crucial role in the patterning and timing of network activity. However, because of their relative inaccessibility, little is known about their development or incorporation into circuits. In this study, we characterized the functional onset, neurotransmitters, rostrocaudal spread, and funicular distribution of one such spinal interneuronal circuit during development. The R-interneuron is the avian homologue of the mammalian Renshaw cell. Both cell types receive input from motoneuron recurrent collaterals and make direct connections back onto motoneurons. By stimulating motoneurons projecting in a given ventral root and recording the response in adjacent ventral roots, we demonstrate that the R-interneuron circuit becomes functional between embryonic day 6 (E6) and E7. This ventral root response is observed at E11 and at E14 until it can no longer be detected at E16. Using bath-applied neurotransmitter receptor antagonists, we were able to demonstrate that the circuit is predominately nicotinic and GABAergic from E7.5 to E15. We also found a glutamatergic component to the pathway throughout this developmental period. The R-interneuron projects three or more segments both rostrally and caudally through the ventrolateral funiculus. The distribution of this circuit may become more locally focused between E7.5 and E15.

2-Amino-5-phosphonovalerate↗
PubMed1989

Identification of excitatory interneurons contributing to generation of locomotion in lamprey: structure, pharmacology, and function.

1. In the in vitro preparation of the lamprey spinal cord, paired intracellular recordings of membrane potential were used to identify interneurons producing excitatory postsynaptic potentials (EPSPs) on myotomal motoneurons. 2. Seventy-nine interneurons (8.4% of all neuron-motoneuron pairs tested) elicited unitary EPSPs that followed one-for-one at short, constant latencies and were therefore considered monosynaptic according to conventional criteria. Evidence was obtained for selectivity and divergence of excitatory interneuron (EIN) outputs and for convergence of EIN input to motoneurons. 3. The neurotransmitter released by EINs may be an excitatory amino acid such as glutamate, because the EPSPs were depressed by antagonists of excitatory amino acids. 4. Intracellular dye injection revealed that EINs have small cell bodies (average 11 x 27 microns), transversely oriented dendrites, and thin (less than 3 microns) slowly conducting axons (0.7 m/s) that project caudally and ipsilaterally. One EIN exhibited a system of thin multi-branching axon collaterals with periodic swellings. Ultrastructurally, these swellings contained clear spherical vesicles, and they apposed postsynaptic membrane specializations. 5. During fictive locomotion, the membrane-potential oscillations of EINs were greater in amplitude than, but similar in shape and timing to, those of their postsynaptic motoneurons. EINs fired action potentials during fictive locomotion and contributed to the depolarization of motoneurons. 6. These interneurons are proposed to be a source of excitation to motoneurons and interneurons in the lamprey spinal cord, participating in motor activity including locomotion.

Action Potentials↗
PubMed1993

The role of interneurons in controlling the tail-withdrawal reflex in Aplysia: a network model.

1. The contributions of monosynaptic and polysynaptic circuitry to the tail-withdrawal reflex in the marine mollusk Aplysia californica were assessed by the use of physiologically based neural network models. Effects of monosynaptic circuitry were examined by the use of a two-layer network model with four sensory neurons in the input layer and one motor neuron in the output layer. Results of these simulations indicated that the monosynaptic circuit could not account fully for long-duration responses of tail motor neurons elicited by tail stimulation. 2. A three-layer network model was constructed by interposing a layer of two excitatory interneurons between the input and output layers of the two-layer network model. These interneurons had properties mimicking those of the recently described interneuron LP117, receiving excitatory input from pleural sensory neurons and evoking a biphasic excitatory postsynaptic potential (EPSP) in pedal motor neurons (Cleary and Byrne 1993). The three-layer model could account for long-duration responses in motor neurons. 3. Sensory neurons are a known site of plasticity in Aplysia. Synaptic plasticity was incorporated into the three-layer model by altering the magnitudes of conductance changes evoked in motor neurons and interneurons by presynaptic sensory neurons. In these simulations the excitatory interneurons converted an amplitude-coded input into an amplitude- and duration-coded output, allowing the three-layer network to support a large range of output amplitudes and durations. 4. Synaptic plasticity at more than one locus modified dramatically the input-output relationship of the three-layer network model. This feature gave the model redundancy in its plastic properties and points to the possibility of distributed memory in the circuitry mediating withdrawal reflexes in Aplysia. Multiple sites of control over the response of the network would likely allow a more diverse repertoire of responses.

Animals↗
PubMed1994

Electrotonic profiles of interneurons in stratum pyramidale of the CA1 region of rat hippocampus.

1. Whole-cell recordings have been made from interneurons located in stratum pyramidale in the CA1 region of the hippocampus. The responses of these interneurons to brief current pulses were recorded; the neurons were filled with biocytin and their morphology was reconstructed. 2. The interneurons were identified as basket cells on the basis of the regional distribution of their axon collateral network and their location in stratum pyramidale. 3. A compartmental model of the reconstructed neuron was made, and the specific membrane resistivity (Rm), specific cytoplasmic resistivity (Ri), and somatic shunt leakage resistance (Rs) determined by adjusting these parameters until an optimal fit was obtained between the compartmental model's current pulse response and the recorded current pulse response of the neuron. 4. This procedure was successful for six neurons, giving Rm from 7 to 66 k omega cm2, Ri from 52 to 484 omega cm, and Rs from 84 M omega to infinity. The specific membrane capacitance was assumed to be 1 microF/cm2. The electrotonic length of the apical dendrites was 1.06 +/- 0.4, and for the basal dendrites it was 0.51 +/- 0.26 (mean +/- SD). 5. Although the total surface area of the interneurons and the physical length of their dendrites was much smaller than for CA1 pyramidal neurons, their electrotonic profiles were similar. Neurons with small physical profiles cannot be assumed to be more electrotonically compact than larger neurons, especially if the dendrites of the smaller neurons have a proportional reduction in diameter. 6. Two neurons did not require a somatic leakage conductance in their electrical representation. This suggests that when a somatic leakage conductance is required, it is an artifact resulting from electrode damage, rather than a requirement caused by a lower resistivity of the somatic membrane compared with the dendritic membrane. 7. Simulations of synaptic currents evoked in the dendrites of these interneurons while the soma is voltage clamped indicate large errors will occur in the time course measurements and amplitude of these currents. Also the ratio of N-methyl-D-aspartate:alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (NMDA:AMPA) currents at these synapses calculated from currents recorded at the soma will be in error because of the differential attenuation of the faster AMPA currents compared with the NMDA currents.

Animals↗
PubMed1994

Synchronous bursting in a subset of interneurons inhibitory to the goldfish Mauthner cell: synaptic mediation and plasticity.

1. Presynaptic activity in the inhibitory network impinging on the Mauthner (M-) cell was investigated in the goldfish medulla in vivo using extra- and intracellular recordings. The inhibitory presynaptic volley elicited by stimulation of the contralateral vestibular nerve consisted of multiple successive peaks at high frequency (up to 1,000 Hz). Less pronounced multicomponent responses were recorded after antidromic activation of the M-cell. Such high-frequency "oscillatory" field potentials also occurred spontaneously. 2. In intracellular recordings, a subset of inhibitory interneurons showed evoked and spontaneous burst discharge. Burst action potentials were correlated with the peaks in the extracellular volley, suggesting that repetitive firing of these cells is synchronized. Nonbursting cells, on the other hand, fired single action potentials in response to vestibular stimuli and were not activated via the M-cell collateral network. 3. Bursting cells were determined morphologically to be part of the feedback inhibitory circuit. Their responses to stimulation of the contralateral vestibular nerve thus suggest the existence of a crossed excitatory pathway to these interneurons. 4. Vestibular-evoked excitatory postsynaptic potentials (EPSPs) in bursting interneurons had a short latency of 0.781 +/- 0.08 ms (mean +/- SD, n = 18) but reached threshold at 2.25 +/- 1 ms (n = 21). These characteristics are suggestive of a chemically mediated EPSP. Indeed, the evoked synchronous repetitive activity of these cells was prevented by superfusion with excitatory amino-acid receptor antagonists. 5. Bursting neurons showed several characteristics that differentiate them from nonbursting cells, including brief action potentials, plateau responses, and intense spontaneous subthreshold activity. 6. With extracellular recordings, tetanization of contralateral vestibular primary afferents evoked a long-lasting potentiation of oscillatory population responses in 11 of 27 cases. Furthermore in three experiments, the frequency of occurrence of spontaneous bursts was enhanced and a similar facilitation was detected at the intracellular level. 7. We conclude that a subset of interneurons in this inhibitory network is capable of repetitive discharges and that evoked as well as spontaneous firing in this population is synchronized. Although electrical coupling between interneurons may mediate synchronization and intrinsic membrane properties may promote burst activity, our data suggest strongly that repetitive firing requires chemically mediated transmission. Furthermore they indicate that the mechanisms underlying evoked as well as spontaneous bursting in this population show activity-dependent plasticity.

Animals↗
PubMed1994

Intersegmental and local interneurons in the metathorax of the stick insect Carausius morosus that monitor middle leg position.

1. In the stick insect, proprioceptive information from the middle leg is used to define the target for the swing movement of the adjacent rear leg ("targeting behavior"). To investigate the underlying neural circuits, intracellular recordings were made in the ganglion controlling the rear leg, the metathoracic ganglion, while systematically moving the tarsus of the middle leg. 2. Several intersegmental interneurons and one local interneuron were identified as possible contributors to the targeting behavior. The intersegmental interneurons code the position of the middle leg tarsus in a highly simplified manner: test movements of the middle leg in the dorsal, lateral, and caudal directions from the standard starting position at right angles to the thorax elicit phasic-tonic responses in three different intersegmental neurons. The response in each interneuron actually reflects the movement and position at only one joint of the middle leg: for the neurons responding primarily to movement in the caudal, dorsal, and lateral test directions, the adequate stimulus is movement at the subcoxal joint, the coxa-trochanter joint, and the femur-tibia joint, respectively. 3. The metathoracic local interneuron integrates information from ipsilateral middle and rear legs in such a way as to provide an approximate measure of the distance between the two tarsi in the longitudinal direction. It is depolarized in a phasic-tonic manner both by caudal movements of the ipsilateral middle leg and by rostral movements of the ipsilateral rear leg. The adequate stimulus in each case is the change in the angle at the subcoxal joint of the leg moved. Depolarization of this neuron activates retractor motoneurons, which is consistent with a role in terminating the swing movement. 4. Altogether the results indicate first, that the targeting behavior could be controlled by very few intersegmental channels and, second, that the nervous system encodes the position of the middle leg tarsus in terms of joint angles rather than in abstract, body-centered coordinates.

Animals↗
PubMed1997

D2 dopamine receptors reduce N-type Ca2+ currents in rat neostriatal cholinergic interneurons through a membrane-delimited, protein-kinase-C-insensitive pathway.

Dopamine has long been known to regulate the activity of striatal cholinergic interneurons and the release of acetylcholine. Yet, the cellular mechanisms by which this regulation occurs have not been elucidated. One way in which dopamine might act is by modulating voltage-dependent Ca2+ channels. To test this hypothesis, the impact of dopaminergic agonists on Ca2+ channels in neostriatal cholinergic interneurons was studied by combined whole cell voltage-clamp recording and single-cell reverse transcription-polymerase chain reactions. Cholinergic interneurons were identified by the presence of choline acetyltransferase mRNA. Nearly, all interneurons tested (90%, n = 17) coexpressed D2 (short and long isoforms) and D1b (D5) dopamine receptor mRNAs. D1a receptor mRNA was found in only a small subset (20%) of the sample and D3 and D4 receptor mRNAs were undetectable. D2 receptor agonists rapidly and reversibly reduced N-type Ca2+ currents. D1b/D1a receptor activation had little or no effect on Ca2+ currents. The D2 receptor antagonist sulpiride blocked the effect of D2 agonists. Dialysis with guanosine-5'-O-(2-thiodiphosphate) or brief exposure to the G protein (Gi/o) alkylating agent N-ethylmaleimide also blocked the D2 modulation. The reduction in N-type currents was neither accompanied by kinetic slowing nor significantly reversed by depolarizing prepulses. The D2 receptor effects were mediated by a membrane-delimited pathway, because the modulation was not seen in cell-attached patches when agonist was applied to the bath and was not disrupted by perturbations in cytosolic signaling pathways known to be linked to D2 receptors. Activation of M2 muscarinic receptors occluded the D2 modulation, suggesting a shared signaling element. However, activation of protein kinase C attenuated the M2 modulation without significantly affecting the D2 modulation. Taken together, our results suggest that activation of D2 dopamine receptors in cholinergic interneurons reduces N-type Ca2+ currents via a membrane-delimited, Gi/o class G protein pathway that is not regulated by protein kinase C. This signaling pathway may underlie the ability of D2 receptors to reduce striatal acetylcholine release.

Animals↗
PubMed1997

Ca2+ ion permeability properties of (R,S) alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in isolated interneurons from the olfactory bulb of the rat.

The aim of the study was to investigate the divalent cation permeability of native alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors expressed in interneurons of the olfactory bulb. Kainic acid (KA) was used as agonist to activate AMPA-receptor-mediated currents, which were recorded with the use of the patch-clamp technique. In interneurons acutely isolated from the olfactory bulb, the current responses to KA showed linear/outwardly rectifying current-voltage (I-V) relationships with a positive average reversal potential of +7 mV in normal external medium (1 mM Ca2+, 1 mM Mg2+). Raising the external Ca2+ concentration to 10 mM suppressed the amplitude, whereas omission of Ca2+ enhanced the amplitude of the current. Spectral analysis of the increase in current variance produced by KA indicated that the decreased amplitude observed in 10 mM Ca2+ was accompanied by a reduction in the apparent single-channel conductance. Raising the concentration of Mg2+ from 1 to 10 mM had a weak depressant effect on the KA-evoked current amplitude. No shift in the reversal potential was observed when the concentration of Ca2+ or Mg2+ was changed from 1 to 10 mM. Increasing the external medium concentration of Ca2+ to 60 mM not only further depressed the amplitudes of the KA-evoked currents but also gave a pronounced leftward shift in the average reversal potential to -32 +/- 9 (SE) mV (N = 7). For neurons in primary culture, current responses to KA also showed linear/outwardly rectifying I-V relationships with a positive average reversal potential in normal external medium. Substituting N-methylglucamine for Na+ and increasing the Ca2+ concentration to 10 mM gave a leftward shift in the average reversal potential from +9 +/- 3 mV to -47 +/- 4 mV (N = 11) and caused a marked reduction in the amplitude of the KA-evoked currents at negative potentials. The permeability properties of the studied AMPA receptors were well predicted by the Eyring rate model (symmetrical, 2 barriers, 1 site). The model gave a pCa2+/pK+ permeability ratio of 0.06 for acutely isolated interneurons and 0.14 for interneurons in primary culture. The constant field theory, which failed to successfully reproduce all the experimental data, gave corresponding low permeability ratios of 0.18 and 0.40 for acutely isolated cells and cells in primary culture, respectively. Thus it is concluded that interneurons in the olfactory bulb mainly express AMPA receptors with low permeability to Ca2+ ions.

Animals↗
PubMed1997

Functional role of Ca2+ currents in graded and spike-mediated synaptic transmission between leech heart interneurons.

We used intracellular recording and single electrode voltage-clamp techniques to explore Ca2+ currents and their relation to graded and spike-mediated synaptic transmissions in leech heart interneurons. Low-threshold Ca2+ currents (activation begins below -50 mV) consist of a rapidly inactivating component (I(CaF)) and a slowly inactivating component (I(CaS)). The apparent inactivation kinetics of I(CaF) appears to be influenced by Ca2+; both the substitution of Ca2+ (5 mM) with Ba2+ (5 mM) in the saline and the intracellular injection of the rapid Ca2+ chelator, bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA), from the recording microelectrode, significantly increase its apparent inactivation time constant. The use of saline with a high concentration of Ba2+ (37.5 mM) permitted exploration of divalent ion currents over a broader activation range, by acting as an effective charge carrier and significantly blocking outward currents. Ramp and pulse voltage-clamp protocols both reveal a rapidly activating and inactivating Ba2+ current (I(BaF)) and a less rapidly activating and slowly inactivating Ba2+ current with a broad activation range (I(BaS)). Low concentrations of Cd2+ (100-150 microM) selectively block I(BaS), without significantly diminishing I(BaF). The current that remains in Cd2+ lacks the characteristic delayed activation peak of I(BaS) and inactivates with two distinct time constants. I(BaF) appears to correspond to a combination of I(CaF) and I(CaS), i.e., to low-threshold Ca2+ currents, that can be described as T-like. I(BaS) appears to correspond to a Ca2+ current with a broad activation range, which can be described as L-like. Cd2+ (100 microM) selectively blocks spike-mediated synaptic transmission between heart interneurons without significantly interfering with low-threshold Ca2+ currents and plateau formation in or graded synaptic transmission between heart interneurons. Blockade of spike-mediated synaptic transmission between reciprocally inhibitory heart interneurons with Cd2+ (150 microM), in otherwise normal saline, prevents the expression of normal oscillations (during which activity in the two neurons consists of alternating bursts), so that the neurons fire tonically. We conclude that graded and spike-mediated synaptic transmission may be relatively independent processes in heart interneurons that are controlled predominantly by different Ca2+ currents. Moreover, spike-mediated synaptic inhibition appears to be required for normal oscillation in these neurons.

Action Potentials↗
PubMed1997

Convergent chemical and electrical synaptic inputs from proprioceptive afferents onto an identified intersegmental interneuron in the crayfish.

Synaptic transmission between proprioceptive afferents from a chordotonal organ in the tailfan of the crayfish and an identified ascending interneuron, interneuron A, in the terminal abdominal ganglion was analyzed. Interneuron A is part of a disynaptic pathway from primary afferent neurons to the lateral giant interneuron involved in producing the characteristic ballistic escape behavior of crayfish. Interneuron A received short and long latency excitatory postsynaptic potentials (EPSPs) from chordotonal afferents. Short latency EPSPs occurred with little central synaptic delay, were unchanged by hyperpolarizing current injection of -2 nA, and remained at a constant amplitude when the nervous system was bathed in saline with a low calcium concentration or saline containing the nicotinic antagonist curare. These EPSPs are thus thought to be mediated by electrical transmission. Longer latency potentials were increased in amplitude by hyperpolarizing current injection, reduced in amplitude when the nervous system was bathed in low-calcium saline, and also reduced by bath application of saline containing curare. These potentials are thus thought to be mediated by chemical transmission. The functional significance of the dual modes of transmission at a key synapse in the escape circuitry is discussed.

Afferent Pathways↗
PubMed1998

Differential regulation of synaptic inputs to dentate hilar border interneurons by metabotropic glutamate receptors.

Regulation of synaptic transmission by metabotropic glutamate receptors (mGluRs) was examined at two excitatory inputs to interneurons with cell bodies at the granule cell-hilus border in hippocampal slices taken from neonatal rats. Subgroup-selective mGluR agonists altered the reliability, or probability of transmitter release, of evoked minimal excitatory synaptic inputs and decreased the amplitudes of excitatory postsynaptic currents (EPSCs) evoked with conventional stimulation. The group II-selective agonist, (2S,1R',2R',3R')-2-(2, 3-dicarboxylcyclopropyl) glycine (DCG-IV; 1 microM), reversibly depressed the reliability of EPSCs evoked by stimulation of the dentate granule cell layer. However, DCG-IV had no significant effect on EPSCs evoked by CA3 stimulation in the majority (82%) of hilar border interneurons. Both the group III-selective agonist, -(+)-2-amino-4-phosphonobutyric acid (-AP4; 3 microM), and the group I-selective agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG; 20 microM) reversibly depressed synaptic input to interneurons from both CA3 and the granule cell layer. We conclude that multiple pharmacologically distinct mGluRs presynaptically regulate synaptic transmission at two excitatory inputs to hilar border interneurons. Further, the degree of mGluR-meditated depression of excitatory drive is greater at synapses from dentate granule cells onto interneurons than at synapses from CA3 pyramidal cells.

Animals↗
PubMed1998

Cooperative mechanisms between leg joints of Carausius morosus II. Motor neuron activity and influence of conditional bursting interneuron.

The activity of the motor neuron pools of the protractor coxae muscle and of the thoracic part of the depressor trochanteris muscle during forward walking in the stick insect was investigated, and a spiking local interneuron, able to produce "endogenous bursting" and innervating both motor neuron pools, was identified. Extracellular recordings of the motor neurons innervating the protractor and the thoracic depressor of front, middle, and rear legs, respectively, were made with oil-hook electrodes from the peripheral nerves nl2c and nl4a while the animals were walking on a styrofoam treadwheel. The corresponding leg movements were registered and phase histograms were created with the software Spike2. Intracellular recordings were made in the neuropile of the metathoracic ganglion with glass electrodes filled with the dye Lucifer yellow. In all three legs measured (front, middle, and rear), both motor neuron pools increased their activity during the swing movement. The increase in the activity of the protractor motor neurons started at the end of the stance approximately 100 ms before reaching the posterior extreme position (PEP), and the activity of the large-sized depressor motor neurons increased as soon as the tarsus was lifted at the PEP. A local spiking interneuron was identified that excited both motor neuron pools. In 4 of 23 recordings the interneuron started to burst in synchrony with protractor and thoracic depressor motor neurons. During bursting a depolarizing stimulus reinforced and a hyperpolarizing stimulus inhibited the activity of both motor neuron pools. Thus we conclude that the thoracic part of the depressor trochanteris muscle might be a component of the neuromuscular system that shapes the swing movement. The two proximal joints, subcoxal and coxa-trochanter, connected mechanically via the thoracic part of the depressor trochanteris muscle, are also connected neurally by segmental and intersegmental spiking interneurons (this paper) and by nonspiking local interneurons (see companion paper).

Animals↗
PubMed1999

Membrane potential and intracellular Ca2+ oscillations activated by mGluRs in hippocampal stratum oriens/alveus interneurons.

Metabotropic glutamate receptors (mGluRs) are expressed heterogeneously in hippocampal interneurons, and their signal transduction cascades remain largely unclear. We characterized an oscillatory response activated by the mGluR agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) in hippocampal interneurons of stratum oriens-alveus (OA) with simultaneous whole cell current-clamp recordings and intracellular Ca2+ imaging with confocal microscopy. 1S,3R-ACPD induced oscillatory membrane depolarizations and rises in intracellular Ca2+ that persisted in tetrodotoxin and were blocked by the antagonist of group I and II mGluRs (S)-alpha-methyl-4-carboxyphenylglycine. Membrane depolarizations and intracellular Ca2+ rises were blocked by extracellular Cd2+ and in Ca2+-free medium. mGluR responses therefore required Ca2+ influx via voltage-gated Ca2+ channels. 1S, 3R-ACPD responses were also antagonized by depleting intracellular stores with thapsigargin and ryanodine, indicating that Ca2+ release from intracellular stores was also necessary. These data suggest that oscillatory responses generated by group I/II mGluRs involve a coupling of Ca2+ entry through voltage-gated Ca2+ channels and Ca2+ release from internal stores. In contrast, 1S,3R-ACPD evoked only smaller depolarizations and intracellular Ca2+ rises, with no oscillations, in other hippocampal interneurons located in or near stratum lacunosum-moleculare. Thus mGluR-mediated oscillatory responses are specifically expressed in certain interneuron subtypes. This heterogeneous expression of glutamate and Ca2+ signaling pathways in specific interneurons may be relevant to their selective vulnerability to excitotoxicity.

Animals↗
PubMed2000

Adenosine receptor expression and modulation of Ca(2+) channels in rat striatal cholinergic interneurons.

Adenosine is a potent regulator of acetylcholine release in the striatum, yet the mechanisms mediating this regulation are largely undefined. To begin to fill this gap, adenosine receptor expression and coupling to voltage-dependent Ca(2+) channels were studied in cholinergic interneurons by combined whole cell voltage-clamp recording and single-cell reverse transcription-polymerase chain reaction. Cholinergic interneurons were identified by the presence of choline acetyltransferase mRNA. Nearly all of these interneurons (90%, n = 28) expressed detectable levels of A(1) adenosine receptor mRNA. A(2a) and A(2b) receptor mRNAs were less frequently detected. A(3) receptor mRNA was undetectable. Adenosine rapidly and reversibly reduced N-type Ca(2+) currents in cholinergic interneurons. The A(1) receptor antagonist 8-cyclopentyl-1, 3-dimethylxanthine completely blocked the effect of adenosine. The IC(50) of the A(1) receptor selective agonist 2-chloro-N6-cyclopentyladenosine was 45 nM, whereas it was near 30 microM for the A(2a) receptor agonist CGS-21680. Dialysis with GDPbetaS or brief exposure to the G protein (G(i/o)) alkylating agent N-ethylmaleimide also blocked the adenosine modulation. The reduction in N-type currents was partially reversed by depolarizing prepulses. A membrane-delimited pathway mediated the modulation, because it was not seen in cell-attached patches when agonist was applied to the bath. Activation of protein kinase C attenuated the adenosine modulation. Taken together, our results argue that activation of A(1) adenosine receptors in cholinergic interneurons reduces N-type Ca(2+) currents via a membrane-delimited, G(i/o) class G-protein pathway that is regulated by protein kinase C. These observations establish a cellular mechanism by which adenosine may serve to reduce acetylcholine release.

Adenosine↗
PubMed2000

Escape swim network interneurons have diverse roles in behavioral switching and putative arousal in Pleurobranchaea.

Escape swimming in the predatory sea slug Pleurobranchaea is a dominant behavior that overrides feeding, a behavioral switch caused by swim-induced inhibition of feeding command neurons. We have now found distinct roles for the different swim interneurons in acute suppression of feeding during the swim and in a longer-term stimulation of excitability in the feeding network. The identified pattern-generating swim neurons A1, A3, A10, and their follower interneuron A-ci1, suppress feeding motor output partly by excitation of the I1 feeding interneurons, which monosynaptically inhibit both the feeding command neurons, PC(P), PSE, and other major interneurons, the I2s. This mechanism exerts broad inhibition of the feeding network suitable to an escape response; broader than feeding suppression in learned and satiation-induced food avoidance and acting through a different presynaptic pathway. Four intrinsic neuromodulatory neurons of the swim network, the serotonergic As1-4, add little to direct suppression of feeding. Rather, they monosynaptically excite the serotonergic metacerebral giant (MCG) neurons of the feeding network, themselves intrinsic neuromodulators of feeding, as well as a cluster of adjacent serotonergic feeding neurons, with both fast and slow EPSPs. They also provide mild neuromodulatory excitation of the PC(P)/PSE feeding command neurons, and I1 and I2 feeding interneurons, which is masked by inhibition during the swim. As1-4 also excite the serotonergic pedal ganglion G neurons for creeping locomotion. These observations further delineate the nature of the putative serotonergic arousal system of gastropods and suggest a central coordinating role to As1-4.

Animals↗
PubMed2000

Properties of a calcium-activated K(+) current on interneurons in the developing rat hippocampus.

Calcium-activated potassium currents have an essential role in regulating excitability in a variety of neurons. Although it is well established that mature CA1 pyramidal neurons possess a Ca(2+)-activated K(+) conductance (I(K(Ca))) with early and late components, modulation by various endogenous neurotransmitters, and sensitivity to K(+) channel toxins, the properties of I(K(Ca)) on hippocampal interneurons (or immature CA1 pyramidal neurons) are relatively unknown. To address this problem, whole-cell voltage-clamp recordings were made from visually identified interneurons in stratum lacunosum-moleculare (L-M) and CA1 pyramidal cells in hippocampal slices from immature rats (P3-P25). A biphasic calcium-activated K(+) tail current was elicited following a brief depolarization from the holding potential (-50 mV). Analysis of the kinetic properties of I(K(Ca)) suggests that an early current component differs between these two cell types. An early I(K(Ca)) with a large peak current amplitude (200.8 +/- 13.2 pA, mean +/- SE), slow time constant of decay (70.9 +/- 3.3 ms), and relatively rapid time to peak (within 15 ms) was observed on L-M interneurons (n = 88), whereas an early I(K(Ca)) with a small peak current amplitude (112.5 +/- 7.3 pA), a fast time constant of decay (39.4 +/- 1.6 ms), and a slower time-to-peak (within 26 ms) was observed on CA1 pyramidal neurons (n = 85). Removal of extracellular calcium or addition of inorganic Ca(2+) channel blockers (cadmium, nickel, or cobalt) was used to demonstrate the calcium dependence of these currents. Addition of norepinephrine, carbachol, and a variety of channel toxins (apamin, iberiotoxin, verruculogen, paxilline, penitrem A, and charybdotoxin) were used to further distinguish between I(K(Ca)) on these two hippocampal cell types. Verruculogen (100 nM), carbachol (100 microM), apamin (100 nM), TEA (1 mM), and iberiotoxin (50 nM) significantly reduced early I(K(Ca)) on CA1 pyramidal neurons; early I(K(Ca)) on L-M interneurons was inhibited by apamin and TEA. Combined with previous work showing that the firing properties of hippocampal interneurons and pyramidal cells differ, our kinetic and pharmacological data provide strong support for the hypothesis that different types of Ca(2+)-activated K(+) current are present on these two cell types.

Aging↗
PubMed2001

Frequency dependence of spike timing reliability in cortical pyramidal cells and interneurons.

Pyramidal cells and interneurons in rat prefrontal cortical slices exhibit subthreshold oscillations when depolarized by constant current injection. For both types of neurons, the frequencies of these oscillations for current injection just below spike threshold were 2--10 Hz. Above spike threshold, however, the subthreshold oscillations in pyramidal cells remained low, but the frequency of oscillations in interneurons increased up to 50 Hz. To explore the interaction between these intrinsic oscillations and external inputs, the reliability of spiking in these cortical neurons was studied with sinusoidal current injection over a range of frequencies above and below the intrinsic frequency. Cortical neurons produced 1:1 phase locking for a limited range of driving frequencies for fixed amplitude. For low-input amplitude, 1:1 phase locking was obtained in the 5- to 10-Hz range. For higher-input amplitudes, pyramidal cells phase-locked in the 5- to 20-Hz range, whereas interneurons phase-locked in the 5- to 50-Hz range. For the amplitudes studied here, spike time reliability was always highest during 1:1 phase-locking, between 5 and 20 Hz for pyramidal cells and between 5 and 50 Hz for interneurons. The observed differences in the intrinsic frequency preference between pyramidal cells and interneurons have implications for rhythmogenesis and information transmission between populations of cortical neurons.

Action Potentials↗
PubMed2006

Scaling of inhibitory interneurons in areas v1 and v2 of anthropoid primates as revealed by calcium-binding protein immunohistochemistry.

Inhibitory GABAergic interneurons are important for shaping patterns of activity in neocortical networks. We examined the distributions of inhibitory interneuron subtypes in layer II/III of areas V1 and V2 in 18 genera of anthropoid primates including New World monkeys, Old World monkeys, and hominoids (apes and humans). Interneuron subtypes were identified by immunohistochemical staining for calbindin, calretinin, and parvalbumin and densities were quantified using the optical disector method. In both V1 and V2, calbindin-immunoreactive neuron density decreased disproportionately with decreasing total neuronal density. Thus, V1 and V2 of hominoids were occupied by a smaller percentage of calbindin-immunoreactive interneurons compared to monkeys who have greater overall neuronal densities. At the transition from V1 to V2 across all individuals, we found a tendency for increased percentages of calbindin-immunoreactive multipolar cells and calretinin-immunoreactive interneurons. In addition, parvalbumin-immunoreactive cell soma volumes increased from V1 to V2. These findings suggest that modifications of specific aspects of inhibition might be critical to establishing the receptive field properties that distinguish visual areas. Furthermore, these results show that phylogenetic variation exists in the microcircuitry of visual cortex that could have general implications for sensory processing.

Animals↗