Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “interneurons”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources

Functional identities of thoracic respiratory interneurones in the cat.

1. Spike-triggered averaging was used to reveal focal synaptic potentials (FSPs) in the thoracic ventral horn resulting from impulses in individual respiratory interneurones situated in the contralateral ventral horn of the same segment (T6 or T7) in anaesthetized paralysed cats. 2. FSPs were of two types, negative-going or positive-going, and were of the same sign at each of several sites for each unit. These two types were interpreted as indicating excitatory or inhibitory actions respectively. 3. The positive-going FSPs were almost all the result of activity in the most strongly modulated, phasic respiratory interneurones, whereas most of the negative-going ones were derived from neurones with a continuous tonic component in their firing patterns. 4. Positive-going FSPs (particularly those from inspiratory neurones) were generally found at more ventral sites in the ventral horn than negative-going ones. 5. It is suggested that an important role for the phasically active interneurones is to provide phasic inhibition, which is combined with largely tonic excitation to produce strong respiratory modulation in the activity of other neurones in the thoracic spinal cord, particularly in motoneurones. However, some groups of respiratory interneurones, such as a group of tonic inspiratory ones which are located more dorsally than the phasic inspiratory ones, may not receive such phasic inhibition.

Action Potentials↗

Synaptic GABAA activation induces Ca2+ rise in pyramidal cells and interneurons from rat neonatal hippocampal slices.

1. Changes in intracellular Ca2+ concentration ([Ca2+]i) induced by activation of GABAA receptors (synaptic stimulation or application of the GABAA agonist isoguvacine) were studied on pyramidal cells and interneurons from hippocampal slices of rats from two age groups (postnatal days (P) 2-5 and P12-13) using the fluorescent dye fluo-3 and a confocal laser scanning microscope. Cells were loaded with the dye either intracellularly, using patch pipettes containing fluo-3 in the internal solution, or extracellularly, using pressure pulses applied to an extracellular pipette containing the permeant dye fluo-3 AM. 2. Interneurons and pyramidal cells from P2-5 slices loaded with fluo-3 AM responded by an increase in [Ca2+]i to isoguvacine and to glutamate, in contrast to cells from P12-13 slices which responded to glutamate but not to isoguvacine. 3. The isoguvacine-induced rise in [Ca2+]i was reversibly blocked by bath application of the GABAA receptor antagonist bicuculline (20 microM), suggesting the specific involvement of GABAA receptors. The sodium channel blocker tetrodotoxin (TTX, 1 microM in the bath) did not prevent the isoguvacine-induced rise in [Ca2+]i. 4. The isoguvacine-induced rise in [Ca2+]i was reversibly blocked by bath application of the calcium channel blocker D600 (50 microM) suggesting the involvement of voltage-dependent Ca2+ channels. 5. Electrical stimulation of afferent fibres induced a transient increase in [Ca2+]i in neonatal pyramidal cells and interneurons (P5) loaded non-invasively with fluo-3 AM. This elevation of [Ca2+]i was reversibly blocked by bicuculline (20 microM) but not by APV (50 microM) and CNQX (10 microM). 6. During simultaneous electrophysiological recording in the current-clamp mode and [Ca2+]i monitoring from P5 pyramidal cells, electrical stimulation of afferent fibres, in the presence of APV (50 microM) and CNQX (10 microM), caused synaptic depolarization accompanied by a few action potentials and a transient increase in [Ca2+]i. In voltage clamp (-70 mV) however, there was no increase in [Ca2+]i following synaptic stimulation, showing that it is depolarization dependent. 7. Using a non-invasive method of [Ca2+]i monitoring, we demonstrate here that in neonatal (P2-5) hippocampus, GABA is an excitatory neurotransmitter which can cause an elevation of [Ca2+]i in interneurons and pyramidal cells via activation of voltage-dependent Ca2+ channels. This action may underlie the trophic role of GABA in hippocampal development.

Animals↗

Osmolarity modulates K+ channel function on rat hippocampal interneurons but not CA1 pyramidal neurons.

1. Whole-cell and single-channel recording methods were used in conjunction with infrared video microscopy techniques to examine the properties of voltage-activated potassium channels in hippocampal neurons during the application of hyposmolar solutions to hippocampal slices from rats. 2. Hyposmolar external solutions (osmolarity reduced by 10% to 267 mosmol l-1) produced a significant potentiation of voltage-activated K+ current on lacunosum/moleculare (L/M) hippocampal interneurons, but not on CA1 and subiculum pyramidal neurons. Hyperpolarization-activated (IH) and leak currents were not altered during the application of hyposmolar solutions in all cell types. 3. Mean channel open time and the probability of channel opening were dramatically increased under hyposmolar recording conditions for outside-out patches from L/M interneurons; no changes were observed for patches from CA1 pyramidal neurons. Mean current amplitude and the threshold for channel activation were not affected by hyposmotic challenge. 4. Hyposmolar external solutions produced a significant reduction in the firing frequency of L/M interneurons recorded in current-clamp mode. Hyposmolar solutions had no effect on resting membrane potential, action potential amplitude or duration, and spike after-hyperpolarization amplitude. 5. These results indicate that selective modulation of interneuron ion channel activity may be a critical mechanism by which osmolarity can regulate excitability in the central nervous system.

Animals↗

Slow excitatory synaptic potentials evoked by distension in myenteric descending interneurones of guinea-pig ileum.

The functional significance of the slow excitatory synaptic potentials (EPSPs) in myenteric neurones is unknown. We investigated this using intracellular recording from myenteric neurones in guinea-pig ileum, in vitro. In all, 121 neurones responded with fast EPSPs to distension of the intestine oral to the recording site. In 28 of these neurones, distension also evoked depolarizations similar to the slow EPSPs evoked by electrical stimulation in the same neurones. Intracellular injection of biocytin and immunohistochemistry revealed that neurones responding to distension with slow EPSPs were descending interneurones, which were immunoreactive for nitric oxide synthase (NOS). Other neurones, including inhibitory motor neurones and interneurones lacking NOS, did not respond to distension with slow EPSPs, but many had slow EPSPs evoked electrically. Slow EPSPs evoked electrically or by distension in NOS-immunoreactive descending interneurones were resistant to blockade of NK(1) or NK(3) tachykinin receptors (SR 140333, 100 nM; SR 142801, 100 nM, respectively) and group I metabotropic glutamate receptors (PHCCC, 10-30 microM), when the antagonists were applied in the recording chamber of a two-chambered organ bath. However, slow EPSPs evoked electrically in inhibitory motor neurones were substantially depressed by SR 140333 (100 nM). Blockade of synaptic transmission in the stimulation chamber of the organ bath abolished slow EPSPs evoked by distension, indicating that they arose from activity in interneurones, and not from anally directed, intrinsic sensory neurones. Thus, distension evokes slow EPSPs in a subset of myenteric neurones, which may be important for intestinal motility.

Animals↗

Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation.

GABAergic interneurones are essential in cortical processing, yet the functional properties of their dendrites are still poorly understood. In this first study, we combined two-photon calcium imaging with whole-cell recording and anatomical reconstructions to examine the calcium dynamics during action potential (AP) backpropagation in three types of V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD). Somatically generated APs actively backpropagated into the dendritic tree and evoked instantaneous calcium accumulations. Although voltage-gated calcium channels were expressed throughout the dendritic arbor, calcium signals during backpropagation of both single APs and AP trains were restricted to proximal dendrites. This spatial control of AP backpropagation was mediated by Ia-type potassium currents and could be mitigated by by previous synaptic activity. Further, we observed supralinear summation of calcium signals in synaptically activated dendritic compartments. Together, these findings indicate that in interneurons, dendritic AP propagation is synaptically regulated. We propose that interneurones have a perisomatic and a distal dendritic functional compartment, with different integrative functions.

Action Potentials↗

Ca2+ imaging of mouse neocortical interneurone dendrites: contribution of Ca2+-permeable AMPA and NMDA receptors to subthreshold Ca2+dynamics.

In this second study, we have combined two-photon calcium imaging with whole-cell recording and anatomic reconstructions to directly characterize synaptically evoked calcium signals in three types of mouse V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD). We observed that subthreshold synaptic activation evoked calcium signals locally restricted to individual dendritic compartments. These signals were mediated by NMDA receptors (NMDARs) in AD and IS cells, whereas in FS cells, calcium-permeable AMPA receptors (CP-AMPARs) provided an additional and kinetically distinct influx. Furthermore, even a single, subthreshold synaptic activation evoked a larger dendritic calcium influx than backpropagating action potentials. Our results demonstrate that NMDARs dominate subthreshold calcium dynamics in interneurones and reveal the functional contribution of CP-AMPARs to a specific subclass of cortical interneurone. These data highlight different strategies in dendritic signal processing by distinct classes of interneurones.

Action Potentials↗

Ca2+ permeability of nicotinic acetylcholine receptors in rat hippocampal CA1 interneurones.

Neuronal nicotinic acetylcholine receptors (nAChRs) are widely expressed in the brain where they are involved in a variety of physiological processes, including cognition and development. The nAChRs are ligand-gated cationic channels, and different subtypes are known to be differentially permeable to Ca2+; the alpha7-containing nAChRs are generally considered to be the most permeable. Ca2+ can activate and regulate a variety of signal transduction cascades, and the influx of Ca2+ through these receptors may have implications for synaptic plasticity. To determine the Ca2+ permeability of the nAChRs in rat hippocampal interneurones in the slice, which contain diverse subtypes of alpha7- and non-alpha7-containing nAChRs, we combined patch-clamp electrophysiology recordings with conventional fura-2 fluorescence imaging techniques. We estimated the relative Ca2+ permeability of the channels by determining the ratio of the increase in [Ca2+]i level (Delta[Ca2+]i) in the soma to the integrated transmembrane current (charge, Q) induced by the activation of the nAChRs, and compared this ratio to the highly Ca2+ permeable NMDA subtype of glutamate receptor channel. In all cells tested, the Delta[Ca2+]i/Q ratio was significantly larger (i.e. more than twice as big) for responses activated by NMDA than for alpha7-containing nAChRs in interneurones; the activation of the non-alpha7 nAChRs did not produce any significant increase in [Ca2+]i. Interestingly, the Ca2+ permeability of native alpha7 nAChRs in PC12 cells was significantly larger than in hippocampal interneurones, and not significantly different from NMDA receptors. Therefore, the alpha7-containing nAChRs in rat hippocampal interneurones are significantly less permeable to Ca2+ than not only NMDA receptors but also alpha7 nAChRs in PC12 cells.

Animals↗

Excitatory effects of serotonin on rat striatal cholinergic interneurones.

We investigated the effects of 5-hydroxytryptamine (5-HT, serotonin) in striatal cholinergic interneurones with gramicidin-perforated whole-cell patch recordings. Bath-application of serotonin (30 microm) significantly and reversibly increased the spontaneous firing rate of 37/45 cholinergic interneurones tested. On average, in the presence of serotonin, firing rate was 273 +/- 193% of control. Selective agonists of 5-HT(1A), 5-HT3, 5-HT4 and 5-HT7 receptors did not affect cholinergic interneurone firing, while the 5-HT2 receptor agonist alpha-methyl-5-HT (30 microm) mimicked the excitatory effects of serotonin. Consistently, the 5-HT2 receptor antagonist ketanserin (10 microm) fully blocked the excitatory effects of serotonin. Two prominent after-hyperpolarizations (AHPs), one of medium duration that was apamin-sensitive and followed individual spikes, and one that was slower and followed trains of spikes, were both strongly and reversibly reduced by serotonin; these effects were fully blocked by ketanserin. Conversely, the depolarizing sags observed during negative current injections and mediated by hyperpolarization-activated cationic currents were not affected. In the presence of apamin and tetrodotoxin, the slow AHP was strongly reduced by 5-HT, and fully abolished by the calcium channel blocker nickel. These results show that 5-HT exerts a powerful excitatory control on cholinergic interneurones via 5-HT2 receptors, by suppressing the AHPs associated with two distinct calcium-activated potassium currents.

Acetylcholine↗

Cell type-specific dependence of muscarinic signalling in mouse hippocampal stratum oriens interneurones.

Cholinergic signalling is critically involved in learning and memory processes in the hippocampus, but the postsynaptic impact of cholinergic modulation on morphologically defined subtypes of hippocampal interneurones remains unclear. We investigated the influence of muscarinic receptor (mAChR) activation on stratum oriens interneurones using whole-cell patch clamp recordings from hippocampal slices in vitro. Upon somatic depolarization, mAChR activation consistently enhanced firing frequency and produced large, sustained afterdepolarizations (ADPs) of stratum oriens-lacunosum moleculare (O-LM) interneurones. In contrast, stratum oriens cell types with axon arborization patterns different from O-LM cells not only lacked large muscarinic ADPs but also appeared to exhibit distinct responses to mAChR activation. The ADP in O-LM cells, mediated by M1/M3 receptors, was associated with inhibition of an M current, inhibition of a slow calcium-activated potassium current, and activation of a calcium-dependent non-selective cationic current (ICAT). An examination of ionic conductances generated by firing revealed that calcium entry through ICAT controls the emergence of the mAChR-mediated ADP. Our results indicate that cholinergic specializations are present within anatomically distinct subpopulations of hippocampal interneurones, suggesting that there may be organizing principles to cholinergic control of GABA release in the hippocampus.

Acetylcholine↗

Muscarinic receptor activation tunes mouse stratum oriens interneurones to amplify spike reliability.

Cholinergic activation of hippocampal targets can initiate and sustain network oscillations in vivo and in vitro, yet the impact of cholinergic modulation on the oscillatory properties of interneurones remains virtually unexplored. Using whole cell current clamp recordings in acute hippocampal slices, we investigated the influence of muscarinic receptor (mAChR) activation on the oscillatory properties of CA1 stratum oriens (SO) interneurones in vitro. In response to suprathreshold oscillatory input, mAChR activation increased spike reliability and precision, and extended the bandwidth that interneurone firing phase-locked. These suprathreshold effects were largest at theta frequencies, indicating that mAChR activation tunes active conductances to enhance firing reliability and precision to theta frequency input. Muscarinic tuning of the intrinsic oscillatory properties of interneurones is a novel mechanism that may be crucial for the genesis of the theta rhythm.

Animals↗

Sorting of striatal and cortical interneurons regulated by semaphorin-neuropilin interactions.

Most striatal and cortical interneurons arise from the basal telencephalon, later segregating to their respective targets. Here, we show that migrating cortical interneurons avoid entering the striatum because of a chemorepulsive signal composed at least in part of semaphorin 3A and semaphorin 3F. Migrating interneurons expressing neuropilins, receptors for semaphorins, are directed to the cortex; those lacking them go to the striatum. Loss of neuropilin function increases the number of interneurons that migrate into the striatum. These observations reveal a mechanism by which neuropilins mediate sorting of distinct neuronal populations into different brain structures, and provide evidence that, in addition to guiding axons, these receptors also control neuronal migration in the central nervous system.

Animals↗

Identified interneurons produce both primary afferent depolarization and presynaptic inhibition.

Crayfish interneurons were identified that appear to be directly responsible for presynaptic inhibition of primary afferent synapses during crayfish escape behavior. The interneurons are fired by a polysynaptic pathway triggered by the giant escape command axons. When directly stimulated, these interneurons produce short-latency, chloride-dependent primary afferent depolarizations and presynaptically inhibit primary afferent input to mechanosensory interneurons.

Action Potentials↗

Spiking local interneurons mediate local reflexes.

A local spiking interneuron in the locust is excited by particular sensory stimulation of a hind leg and forms an inhibitory connection with one hind leg motor neuron. Its behavioral effect is to mediate a local postural reflex. This interneuron is one of a population of interneurons with similar morphology and physiology that participate in the same local circuits as the better known nonspiking local interneurons.

Animals↗

Force-sensitive interneurons in the spinal cord of the cat.

The input-output properties of interneurons mediating spinal reflexes were investigated by extracellularly recording the response of interneurons to excitation from muscle receptors in the ankle extensor muscles of decerebrated, spinal cats. A population ofinterneurons in the intermediate region ofthe spinal cord is potently excited by increases in muscle force. Unlike the discharge of Golgi tendon organs, which accurately encodes moment-to-moment variations in the force of a single muscle, the discharge of these interneurons depends in a dynamic and usually nonlinear way on the force in several muscles. Powerful input from unidentified mechanoreceptors in muscle, presumably free nerve endings, is at least partly responsible for these properties. These force-sensitive interneurons are more likely to mediate clasp knife-type inhibition than simple negative force feedback.

Animals↗

Regulation of excitatory neural input to longitudinal intestinal muscle by myenteric interneurons.

The circuit of myenteric interneurons that regulate excitatory input to longitudinal colonic muscle was identified using dispersed ganglia and longitudinal muscle strips with adherent myenteric plexus from rat distal colon. The preparations enabled measurement of neurotransmitter release from interneurons and/or excitatory motoneurons innervating longitudinal muscle. 1, 1-Dimethyl-4-phenylpiperizinium (DMPP) and somatostatin were used to activate myenteric neurons in dispersed ganglia and muscle strips, respectively. DMPP-stimulated vasoactive intestinal peptide (VIP) release in dispersed ganglia was inhibited by [Met]enkephalin and bicuculline and augmented by naloxone and GABA, implying that inhibitory opioid and stimulatory GABA neurons regulate the activity of VIP interneurons. In muscle strips, VIP stimulated basal and augmented somatostatin-induced substance P (SP) release; the somatostatin-induced increase in SP release was inhibited by VIP-(10-28) and NG-nitro-L-arginine, implying that excitatory VIP neurons regulate tachykinin motoneurons innervating longitudinal muscle. Somatostatin inhibited [Met]enkephalin and stimulated VIP release; basal and somatostatin-stimulated VIP release were inhibited by [Met]enkephalin and bicuculline and augmented by naloxone and GABA, implying that inhibitory pathways linking somatostatin, opioid, and GABA neurons regulate VIP interneurons, which in turn regulate tachykinin and probably cholinergic motoneurons.

Animals↗

Voltage-controlled plasticity at GluR2-deficient synapses onto hippocampal interneurons.

High-frequency stimulation of pyramidal cell inputs to developing (P9-12) hippocampal stratum radiatum interneurons expressing GluR2-lacking, Ca(2+)-permeable AMPA receptors produces long-term depression of synaptic transmission, if N-methyl-d-aspartate (NMDA) receptors are blocked. Here we show that these same synapses display a remarkably versatile signal integration if postsynaptic NMDA receptors are activated. At synapses expressing GluR2-deficient AMPA receptors, tetanic stimulation that activates NMDA receptors triggered long-term potentiation or depression (LTP or LTD) depending on membrane potential. LTP was elicited at most synapses when the interneuron was held at -30 mV during the stimulus train but was typically prevented by postsynaptic hyperpolarization to -70 mV, by strong depolarization to 0 mV, by d-2-amino-5-phosphonovaleric acid, or by postsynaptic injection of the Ca2+ chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid. At synapses with predominantly GluR2-containing AMPA receptors, repetitive stimulation did not change synaptic strength regardless of whether NMDA receptors were activated. The interactions among GluR2 expression, NMDA receptor expression, and membrane potential thus confer on hippocampal interneurons a distinctive means for differential decoding of high-frequency inputs, resulting in enhanced or depressed transmission depending on the functional state of the interneuron.

Animals↗

GABA application to hippocampal CA3 or CA1 stratum lacunosum-moleculare excites an interneuron network.

Whole cell voltage-clamp recording and focal application of the neurotransmitter gamma-aminobutyric acid (GABA) were used to investigate the ability of exogenous GABA applied to different locations within the guinea pig hippocampal slice to trigger a giant GABA-mediated postsynaptic current (GPSC) in pyramidal cells. A GPSC reflects the synchronous release of GABA from a group of interneurons. Recordings were done in the presence of 4-aminopyridine (4-AP) and blockers of ionotropic glutamatergic synaptic transmission. Spontaneous GPSCs occurred rhythmically in pyramidal cells under these conditions. Brief focal pressure application of GABA (500 microM; 30-200 ms) to CA3 stratum lacunosum-moleculare (SLM) or to the border between CA3 s. radiatum (SR) and SLM triggered an "all-or-none" GPSC in CA3 and CA1 pyramidal cells that looked like the spontaneous GPSCs. During the refractory period following a spontaneous GPSC, application of GABA could not trigger a GPSC. Both spontaneous GPSCs and GPSCs triggered by exogenous GABA were blocked by suppressing synaptic transmission with high Mg(2+)/low Ca(2+) bath solution. On the other hand, focal application of GABA to CA3 s. oriens (SO) or to proximal SR did not trigger a GPSC in the CA3 pyramidal cell; instead it produced a graded response. Focal application of GABA to regions other than CA3 was also tested. Focal application of GABA to CA1 SLM always triggered a GPSC in the CA3 pyramidal cell. Focal application of GABA within the outer two-thirds of the dentate molecular layer often elicited a GPSC in the CA3 pyramidal cell. In contrast, focal application of GABA to CA1 SO, to CA1 SR, or to the hilus elicited no current response in the CA3 pyramidal cell. These data indicate that the GPSC recorded in pyramidal cells that was triggered by focal GABA application resulted from the synchronous synaptic release of GABA from activated interneurons rather than from the binding of exogenous GABA to receptors on the pyramidal cell. Furthermore, the "all-or-none" nature of the response to SLM GABA applications of different durations indicates that the exogenous GABA was exciting (directly or indirectly) some members of a network of interneurons, which in turn recruited the rest of the network, rather than individually activating each interneuron that contributed to the GPSC. Interestingly, the effective sites of GABA application--CA3 SLM, CA1 SLM, and the outer two-thirds of the dentate molecular layer--are also the sites which receive direct innervation from the entorhinal cortex in an intact animal.

Animals↗

Comparison of the morphological and electrotonic properties of Renshaw cells, Ia inhibitory interneurons, and motoneurons in the cat.

The morphological and electrotonic properties of 4 motoneurons, 8 Ia inhibitory interneurons, and 4 Renshaw cells were compared. The morphological analysis, based on 3-D reconstructions of the cells, revealed that dendrites of motoneurons are longer and more extensively branched. Renshaw cells have dendrites that are shorter and simpler in structure. Dendrites of Ia inhibitory interneurons could be as long as those of motoneurons but the branching structure resembled that of Renshaw cells. Compartmental models were used to determine the electrotonic properties of the paths from each dendritic terminal to the soma. The attenuations of steady-state voltage changes in motoneurons were 3 and 7 times larger than in Ia inhibitory interneurons and Renshaw cells, respectively. The same relative order was observed for current attenuation and electrotonic length. The dendritic input resistances in Renshaw cells were 2 and 4 times larger than in Ia inhibitory interneurons and motoneurons, respectively. The difference in these electrotonic properties increased during higher synaptic activity as modeled by a decrease of Rm. The peak amplitudes of voltage transients at sites of brief, synaptic-like changes in conductance were highly dependent on cell class and were largest in Renshaw cells and smallest in motoneurons. In combination with class-specific differences in the attenuation of transient voltage signals, this led to large differences in the peak amplitudes of somatic voltage transients. Differences in the rise times and half-widths of the voltage transients were observed as well. Thus, based on passive properties, each cell class has a unique set of input/output properties.

Animals↗