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PubMed2001

Evx1 is a postmitotic determinant of v0 interneuron identity in the spinal cord.

Interneurons in the ventral spinal cord are essential for coordinated locomotion in vertebrates. During embryogenesis, the V0 and V1 classes of ventral interneurons are defined by expression of the homeodomain transcription factors Evx1/2 and En1, respectively. In this study, we show that Evx1 V0 interneurons are locally projecting intersegmental commissural neurons. In Evx1 mutant embryos, the majority of V0 interneurons fail to extend commissural axons. Instead, they adopt an En1-like ipsilateral axonal projection and ectopically express En1, indicating that V0 interneurons are transfated to a V1 identity. Conversely, misexpression of Evx1 represses En1, suggesting that Evx1 may suppress the V1 interneuron differentiation program. Our findings demonstrate that Evx1 is a postmitotic determinant of V0 interneuron identity and reveal a critical postmitotic phase for neuronal determination in the developing spinal cord.

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PubMed2007

Impaired firing and sodium channel function in CA1 hippocampal interneurons after transient cerebral ischemia.

Although interneurons in area CA1 of the hippocampus are less vulnerable to cerebral ischemia than CA1 pyramidal cells, it is not clear whether their relatively intact cellular morphology implies preservation of normal function. As maintenance of cellular excitability and firing properties is essential for interneurons to regulate neural networks, we investigated these aspects of interneuronal function after transient cerebral ischemia in rats. Cerebral ischemia in rats was induced for 8 mins by a combination of bilateral common carotid artery occlusion and hypovolemic hypotension, and whole cell patch clamp recordings were made in hippocampal slices prepared 24 h after reperfusion. Interneurons located within stratum pyramidale of area CA1 exhibited normal membrane properties and action potentials under these conditions. However, their excitability had declined, as evidenced by an increased action potential threshold and a rightward shift in the relationship between injected depolarizing current and firing rate. Voltage-clamp experiments revealed that transient cerebral ischemia reduced the peak Na(+) current and shifted Na(+) channel activation to more depolarized values, but did not alter steady-state inactivation of the channel. Double immunofluorescence cytochemistry showed that transient cerebral ischemia also reduced Na(v)1.1 subunit immunoreactivity in interneurons that coexpressed parvalbumin. We conclude that transient cerebral ischemia renders CA1 interneurons less excitable, that depressed excitability involves impaired Na(+) channel activation and that Na(+) channel dysfunction is explained, at least in part, by reduced expression of the Na(v)1.1 subunit. These changes may promote interneuron survival, but might also contribute to pyramidal cell death.

Action Potentials↗

PubMed2000

Networks of interneurons with fast and slow gamma-aminobutyric acid type A (GABAA) kinetics provide substrate for mixed gamma-theta rhythm.

During active exploration, hippocampal neurons exhibit nested rhythmic activity at theta ( approximately 8 Hz) and gamma ( approximately 40 Hz) frequencies. Gamma rhythms may be generated locally by interactions within a class of interneurons mediating fast GABA(A) (GABA(A,fast)) inhibitory postsynaptic currents (IPSCs), whereas theta rhythms traditionally are thought to be imposed extrinsically. However, the hippocampus contains slow biophysical mechanisms that may contribute to the theta rhythm, either as a resonance activated by extrinsic input or as a purely local phenomenon. For example, region CA1 of the hippocampus contains a slower class of GABA(A) (GABA(A,slow)) synapses, believed to be generated by a distinct group of interneurons. Recent evidence indicates that these GABA(A,slow) interneurons project to the GABA(A, fast) interneurons that contribute to hippocampal gamma rhythms. Here, we use biophysically based simulations to explore the possible ramifications of interneuronal circuits containing separate classes of GABA(A,fast) and GABA(A,slow) interneurons. Simulated interneuronal networks with fast and slow synaptic kinetics can generate mixed theta-gamma rhythmicity under restricted conditions, including strong connections among each population, weaker connections between the two populations, and homogeneity of cellular properties and drive. Under a broader range of conditions, including heterogeneity, the networks can amplify and resynchronize phasic responses to weak phase-dispersed external drive at theta frequencies to either GABA(A,slow) or GABA(A,fast) cells. GABA(A, slow) synapses are necessary for this process of amplification and resynchronization.

Algorithms↗

PubMed2005

Properties of excitatory synaptic responses in fast-spiking interneurons and pyramidal cells from monkey and rat prefrontal cortex.

In the prefrontal cortex (PFC) during working memory tasks fast-spiking (FS) interneurons might shape the spatial selectivity of pyramidal cell firing. In order to provide time control of pyramidal cell activity, incoming excitatory inputs should excite FS interneurons more vigorously than pyramidal cells. This can be achieved if subthreshold excitatory responses of interneurons are considerably stronger and faster than those in pyramidal neurons. Here we compared the functional properties of excitatory post-synaptic potentials (EPSPs) between pyramidal cells and FS interneurons in slices from monkey dorsolateral PFC and rat prelimbic cortex. Miniature, unitary (in connected pairs or by minimal stimulation) and compound (evoked by electrical stimulation of the white matter) EPSPs were recorded in whole cell mode. We found that EPSPs were significantly larger and faster in FS interneurons than those recorded from pyramidal cells, consistent with the idea of more efficient recruitment of FS interneurons compared to pyramidal neurons. Similar results were obtained in monkey and rat PFC, suggesting a stable role of FS interneurons in this circuitry across species.

Action Potentials↗

PubMed2006

Migratory response of interneurons to different regions of the developing neocortex.

The interactions between migrating interneurons and their environment that lead to stereotypic migration pathways remain largely undefined. We have used time-lapse imaging to record the migratory responses of labeled interneurons to different regions of the migratory pathway in organotypic slice cultures. We tested the hypothesis that the length of the migratory pathway is not equally permissive for interneuron migration, with separate zones of inhibition and attraction. Three different experimental approaches were used to address this issue, including explant cocultures, cortical overlay cultures, and rotation of cortical slices. The results clearly identify the lateral region to be an attractive substrate for interneuron entry at embryonic day 12.5, whereas the medial region at this stage contains a zone of inhibition. This property of the medial neocortex is temporally regulated with switching from inhibition to attraction within 24 h. We suggest that this temporal regulation may provide a mechanism for gating the entry of interneurons into the hippocampus while ensuring that cortical interneurons are properly confined within the neocortical wall. In this manner, interneurons arising from common precursors and sharing common migratory pathways are able to populate different pallial structures.

Aging↗

PubMed2006

Dopamine increases inhibition in the monkey dorsolateral prefrontal cortex through cell type-specific modulation of interneurons.

Dopaminergic modulation of the dorsolateral prefrontal cortex (DLPFC) plays an important role in cognitive functions, including working memory. At optimal concentrations, dopamine (DA) enhances pyramidal cell (PC) firing to increase task-related activity. However, spatial and temporal "tuning" of the persistent firing that underlies this mnemonic activity requires inhibitory control from gamma-aminobutyric acidergic (GABAergic) interneurons. How DA modulates the inhibitory control provided by different types of interneurons in the primate cortex is not known. We studied the effects of DA and DA receptor-specific agonists and antagonists on GABAergic inhibition and interneuron excitability in slices from primate DLPFC. Using whole-cell voltage-clamp recordings from layer 2/3 pyramidal neurons, we examined the effects of DA on spontaneous (action potential dependent) and miniature (action potential independent) inhibitory postsynaptic currents. We found that DA can increase inhibition via a presynaptic, action potential-dependent mechanism. In current-clamp recordings from physiologically and morphologically identified interneurons, we investigated the pharmacology and cell type specificity of this effect. DA increased the excitability of fast-spiking (FS), nonadapting interneurons via activation of D1- but not D2-type receptors. In contrast, DA had no effect on interneurons with adapting firing patterns. Thus, DA and D1 receptor activation affect local recurrent circuits by selectively modulating FS interneurons that control the firing of PCs through perisomatic innervation.

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PubMed2006

Age-related changes in striatal nitric oxide synthase-immunoreactive interneurones in the dystonic dtsz mutant hamster.

The dt(sz) mutant hamster represents a model of paroxysmal dyskinesia in which dystonic episodes can be age-dependently induced by stress. GABAergic interneurones which co-express calcium binding proteins were found to be reduced in the striatum of the dt(sz) mutant. Other types of striatal interneurones have so far not been examined. In the present study, we therefore determined the density of nitric oxide synthase (NOS)-immunoreactive interneurones in the striatum of the dt(sz) mutant in comparison with nondystonic control hamsters. At the age of most marked expression of dystonia (30-40 days of life), the density of NOS-positive interneurones was decreased in the striatum of dt(sz) hamsters (-21%) in comparison with age-matched nondystonic control hamsters. Spontaneous remission of dystonia (age >90 days) coincided with a normalization of the density of NOS-reactive interneurones within the whole striatum of dt(sz) hamsters, but there remained a reduced density in distinct subregions. Together with previous findings the present data indicate that the development of striatal interneurones is retarded in mutant hamsters. The age-related deficit of NOS-reactive interneurones may at least in part contribute to an abnormal activity of striatal GABAergic projection neurones and thereby to the age-dependent dystonic syndrome in the dt(sz) mutant.

Age Factors↗

PubMed1995

The influence of premotor interneuron populations on the frequency of the spinal pattern generator for swimming in Xenopus embryos: a simulation study.

Our aim was to test the hypothesis that the frequency of neuronal rhythm-generating networks is partly controlled by the size of the active premotor interneuron population. We have tested possible mechanisms for frequency changes in a population model of the Xenopus laevis embryo spinal rhythm-generating networks for swimming. After initiation by a brief sensory excitation, the frequency of swimming activity decreases to a steady level determined by the properties of the 24 interneurons and their connections. The initial frequency decrease was dependent on the time-course of initiating sensory synaptic excitation. When some premotor excitatory interneurons were given weaker synaptic connections to reflect the variability in the spinal cord, they could drop out and stop firing during the initial frequency decrease while swimming activity continued. If the synaptic input of such weak excitatory interneurons was graded finely, they could drop out consecutively. This led to further decreases in the level of tonic excitation and in network frequency which depended on the number, type and distribution of excitatory interneurons that stopped firing. Silent weak excitatory interneurons could be recruited by a second sensory excitation and cause an increase in tonic depolarization and frequency which outlasted the sensory input. Such recruitment could occur on both sides after local sensory stimulation to only one region or one side of the model. We conclude that these computer simulations support the hypothesis that premotor interneuron drop-out and recruitment is one mechanism which can control frequency in a locomotor central pattern generator.

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PubMed2004

Enteric motor and interneuronal circuits controlling motility.

The enteric nervous system regulates intestinal motility. It contains intrinsic sensory neurones, several types of interneurones and excitatory and inhibitory motor neurones. This review summarizes our knowledge of motor neurones and interneurones in simple motility reflex pathways (ascending and descending excitation, descending inhibition) and it focuses on guinea-pig ileum. Excitatory circular muscle motor neurones contain choline acetyltransferase (ChAT) and tachykinins and project orally 0.5-10 mm. They transmit via muscarinic acetylcholine receptors and tachykinins acting at NK1 and NK2 receptors. Inhibitory circular muscle motor neurones contain nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP), project anally up to 25 mm and transmit via ATP, nitric oxide and/or VIP. Ascending interneurones project up to 10 mm orally and contain ChAT and tachykinins. They transmit to each other via ACh at nicotinic receptors (nAChR), but to excitatory motor neurones via both nAChR and NK3 receptors. There are at least three types of descending interneurones and one transmits to inhibitory motor neurones via ATP acting at P2X receptors. NOS-containing descending interneurones receive input via P2Y receptors from other interneurones. Transmission to and from the other descending interneurones (ChAT/5-HT, ChAT/somatostatin) is yet to be characterized.

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PubMed1971

Recurrent inhibition of interneurones monosynaptically activated from group Ia afferents.

1. Interneurones monosynaptically excited from large muscle spindle (Ia) afferents and inhibited from motor axon collaterals were searched for in the lumbar spinal cord of the cat.2. Monosynaptic Ia excitation was found in sixty-seven of sixty-nine interneurones inhibited by antidromic volleys. These interneurones were excited from Ia afferents from one or a few muscles (mainly close synergists). Volleys in high threshold muscle and skin afferents (FRA) evoked polysynaptic excitation or inhibition. Weak inhibition from Ia afferents (from antagonists to those giving Ia excitation) was seen in a few cells. Monosynaptic excitation was evoked from the ventral quadrant of the spinal cord and polysynaptic excitation from the dorsal quadrant.3. Inhibition from motor axon collaterals was evoked with a latency (1.2-2.0 msec) suggesting a disynaptic linkage and had the same time course as in motoneurones. It prevented synaptic activation of 60% of interneurones and decreased the firing index and delayed generation of spikes in the remaining.4. The interneurones with convergence of monosynaptic Ia excitation and inhibition from motor axon collaterals were found in the ventral horn dorsomedial to motor nuclei. No inhibition by antidromic volleys could be detected in interneurones located in intermediate nucleus and activated monosynaptically from Ia, Ib, group I or cutaneous afferents.5. It was concluded that the ventral Ia interneurones inhibited by volleys in recurrent motor axon collaterals mediate the reciprocal Ia inhibition to motoneurones.

Action Potentials↗

PubMed1972

Synaptic actions of single interneurones mediating reciprocal Ia inhibition of motoneurones.

1. The investigation was aimed at defining the function of the interneurones which, according to indirect evidence, mediate the reciprocal Ia inhibition of motoneurones (Hultborn, Jankowska & Lindstrom, 1971 b) by studying their direct synaptic actions. These actions were tested by recording post-synaptic potentials in motoneurones following spike activity of single interneurones activated by iontophoretic application of glutamate. The interneurones were found to produce unitary monosynaptic IPSPs in those motoneurones in which disynaptic IPSPs are evoked by the group Ia afferents which monosynaptically excite the interneurones.2. Unitary IPSPs were found in more than 80% of the motoneurones impaled in the immediate vicinity of the axonal branches of the investigated Q interneurones in the PBSt motor nucleus. It is estimated that each interneurone might inhibit about every fifth PBSt motoneurone. The amplitudes of the unitary IPSPs ranged between 8 and 220 muV and were 10-200 times smaller than the maximal Ia IPSPs evoked in the same motoneurones.3. The synaptic delay in the generation of unitary IPSPs was measured in relation to the spike potentials recorded from the terminal branches of interneurones in the immediate vicinity of the impaled motoneurones. The synaptic delays ranged between 0.28 and 0.42 msec.4. From chloride reversal tests and an analysis of the time course of the unitary IPSPs it was concluded that the terminals of the investigated interneurones make synaptic contact predominantly on the soma and/or on the proximal parts of the dendrites of the motoneurones, their distribution being, however, not quite uniform.

Action Potentials↗

PubMed1983

Inhibition of dorsal spinocerebellar tract cells by interneurones in upper and lower lumbar segments in the cat.

The topographical distribution of interneurones mediating disynaptic inhibition of dorsal spinocerebellar tract (d.s.c.t.) cells from group I muscle afferents in the cat was investigated using both physiological and morphological techniques. Lesions of either the dorsal funiculi or of the lateral and ventral funiculi were made between L4 and L5 segments in two groups of cats. I.p.s.p.s. evoked from group I afferents were seen after both these lesions, showing that the i.p.s.p.s were evoked by interneurones located more caudally as well as by interneurones in the same segments as Clarke's column. Distribution of the caudally located interneurones in the lower lumbar segments was investigated after marking these interneurones with horseradish peroxidase retrogradely transported from Clarke's column. The horseradish peroxidase was injected along L3-L4 segments of Clarke's column in two cats with transected dorsal funiculi. The marked cells were found in L5, L6, L7 and S1 segments, with a highest density in L6 and L7. They were seen in laminae V, VI and VII. A search was made for interneurones which could be antidromically invaded following stimuli applied in Clarke's column and were monosynaptically excited by group I afferents. Such interneurones were found at locations corresponding to laminae V-VI of Rexed. The latencies of antidromic and orthodromic responses were within ranges allowing them to mediate disynaptic inhibition of d.s.c.t. cells.

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PubMed1984

Inhibition from the brain stem of inhibitory interneurones of the cat's dorsal lateral geniculate nucleus.

Brain-stem control of inhibitory circuits in the dorsal lateral geniculate nucleus (d.l.g.n.) of the cat was studied with extracellular recordings from functionally identified interneurones and with intracellular recordings from principal cells. Perigeniculate neurones, the recurrent inhibitory interneurones of the d.l.g.n., were inhibited by low-threshold stimulation within a wide bilateral field of the brainstem reticular formation extending from the rostral mesencephalon to the caudal medulla oblongata. The inhibition had a latency of 10-12 ms for stimulation sites in the mesencephalon and a duration of about 100 ms. The brain-stem stimulation evoked large hyperpolarizing potentials in intracellularly recorded perigeniculate neurones, indicating that the effect was due to post-synaptic inhibition. Intrageniculate interneurones, the feed-forward inhibitory interneurones of the d.l.g.n., were inhibited with a similar time course from the same region of the brain stem. Both feed-forward and recurrent inhibitory post-synaptic potentials (i.p.s.p.s) in principal cells were depressed by a preceding stimulation of brain-stem sites effective for the interneurones. The depression had about the same time course as the inhibition of the interneurones and it occurred without a concomitant change in the membrane potential of the recorded principal cells. A small depolarizing potential, with a latency of 10-20 ms, was observed in some principal cells after brain-stem stimulation. The potential reversed polarity when i.p.s.p.s were reversed by current injection into the recorded cell indicating that it was due to disinhibition of the principal cells. The possible neuronal pathway for the inhibition of the d.l.g.n. in interneurones is considered and it is proposed that the effect is mediated by a group of neurones located in the caudal mesencephalon and the rostral pons close to the fibres of the brachium conjunctivum.

Action Potentials↗

PubMed1984

Receptive fields of cricket giant interneurones are related to their dendritic structure.

The structural relationship between the afferent projection and the dendrites of the interneurones was examined in the cercal-to-giant interneurone system of the cricket using intracellular recording and dye injection techniques. The physiology of the sensory neurones beneath the cercal filiform hairs was investigated by placing a recording pipette over the end of a cut hair and using movements of the pipette to characterize the directionality of the receptor. Most of the filiform receptors could be classified as belonging to one of four major types. Each type is sensitive to a different wind direction and is confined to particular regions of the cercus. The location of the terminal arborizations of each type of sensory cell was revealed by staining with cobalt chloride. Single cells were stained reliably by placing a dye-filled pipette over a cut hair. Each physiological receptor type arborizes in a different region of the central nervous system. Therefore the neuropile is functionally divided according to wind direction. The dendrites of three identified interneurones were examined in the context of this afferent projection. It was found that each of these neurones has dendrites in regions of neuropile corresponding to different wind directions. By searching for unitary synaptic potentials in identified interneurones, it was possible to show a strong correlation between anatomical overlap of primary afferent and interneurone and the existence of a synaptic connexion. Further, when there was no overlap, no synaptic potentials were seen. Therefore the over-all excitatory receptive field of an interneurone could be predicted by examining its dendritic structure. Each of the three identified interneurones examined in this study was found to have a directional response that matched the response predicted on the basis of its anatomy.

Action Potentials↗

PubMed1988

Enkephalin hyperpolarizes interneurones in the rat hippocampus.

1. Intracellular recordings were made from pyramidal cells and from electrophysiologically identified interneurones in the CA1 region of the hippocampal slice preparation from the rat. 2. Enkephalin blocked the hyperpolarization of pyramidal cells evoked by application of glutamate to synaptically coupled inhibitory interneurones. 3. Enkephalin hyperpolarized interneurones, most probably by increasing potassium conductance; this action was blocked by the opiate antagonist, naloxone. 4. Activation of gamma-aminobutyric acid(B) receptors with baclofen in interneurones produced a similar hyperpolarization that was resistant to naloxone. 5. In addition to hyperpolarizing interneurones, enkephalin blocked the inhibitory postsynaptic potential recorded in these cells. 6. These results suggest that opiate receptors are selectively localized on inhibitory interneurones in the hippocampus and are coupled to potassium channels. Activation of these receptors causes a disinhibition of both pyramidal cells and inhibitory interneurones.

Action Potentials↗

PubMed1988

The ascending projection of interneurones activated by group I muscle afferent fibres of the cat hindlimb.

1. The level of the ascending projection of lumbosacral interneurones with a monosynaptic input from group I muscle afferents of the cat hindlimb has been investigated. The study was concerned particularly with the interneurones mediating group I non-reciprocal inhibition of motoneurones. 2. In chloralose-anaesthetized cats, single-unit microelectrode recordings were made, in the lateral funiculus at L6, from the ascending axons of lumbosacral interneurones. The axons studied were discharged by group I afferents primarily from extensor muscles of the knee and ankle. Some units were discharged in addition by cutaneous and/or joint afferents. 3. The extent of the ascending projection of the interneurones was assessed by antidromic activation of their axons in the lateral funiculus at different spinal levels. The great majority of axons tested (thirty-four out of thirty-six) were found to have an ascending projection to at least the L4 level and of these most (90%) did not project beyond the L4 or L3 segments of the cord. 4. The projection to at least L4, together with monosynaptic input from group I afferents and a pattern of peripheral input characteristic of interneurones in laminae V-VI of lumbosacral segments, identified thirty-four of the thirty-six units as interneurones mediating group I non-reciprocal inhibition. 5. These results suggest that the ascending group I inhibitory pathway, formed by these interneurones, is associated specifically with the group I relay of the dorsal spinocerebellar tract in Clarke's column, rather than being conterminous with group I afferents, which project throughout the rostral lumbar and lowest thoracic segments.

Animals↗

PubMed1992

Monosynaptic EPSPs elicited by single interneurones and spindle afferents in trigeminal motoneurones of anaesthetized rats.

1. Our aim has been to quantify the monosynaptic connections of trigeminal interneurones and spindle afferents onto jaw-elevator motoneurones as a step towards identifying common features in organization of monosynaptic inputs onto motoneurones. We have used the intracellular variant of the spike-triggered averaging method to examine the connections of single identified trigeminal interneurones and jaw-elevator muscle spindle afferents onto single jaw-elevator motoneurones. The interneurones examined lay in the region immediately caudal to the trigeminal motor nucleus. The experiments were performed on rats anaesthetized with pentobarbitone, paralysed and artificially ventilated. 2. Ten EPSPs and eight IPSPs were obtained from examining the connections of seventeen interneurones to thirty-six motoneurones, suggesting a functional connectivity of 50% for individual interneurones onto elevator motoneurones. Fourteen EPSPs were obtained from examining the connections of thirteen spindle afferents onto twenty-seven motoneurones, giving a functional connectivity of 52% for individual spindle afferents onto elevator motoneurones. The amplitudes of the EPSPs elicited by interneurones ranged from 7-48 microV (mean = 17, S.D. = 12.5, n = 10) and from 7 to 289 microV (mean = 64, S.D. = 76.0, n = 14) for the spindle-mediated EPSPs; the difference in the two means was not significant (P = 0.07). 3. However, the amplitude of averaged responses obtained by signal averaging methods are dependent on the assumption that the postsynaptic response occurs following every impulse in the presynaptic neurone. We therefore estimated the percentage of sweeps which contained EPSPs triggered by the presynaptic neurone under study. In essence the method used consisted of visual inspection of the individual sweeps comprising an average in order to assess the occurrence of EPSPs within six separate time windows, each of duration +/- 0.3 ms. Five windows were placed at randomly selected times on average and were used to provide an estimate of the frequency of occurrence of randomly triggered EPSPs. The sixth window was centred on the start of the averaged EPSP and the frequency of occurrence of randomly triggered EPSPs was subtracted from the frequency of occurrence of EPSPs in this window to produce an estimate of the incidence of EPSPs triggered by the presynaptic neurone under study. 4. Values of the incidence of occurrence of EPSPs triggered by the presynaptic neurones ranged from 4.3 to 92% for the fifteen averaged EPSPs which could be analysed in this manner (two elicited by interneurones and thirteen by spindle afferents).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2006

mGluR1/5 subtype-specific calcium signalling and induction of long-term potentiation in rat hippocampal oriens/alveus interneurones.

Hippocampal inhibitory interneurones demonstrate pathway- and synapse-specific rules of transmission and plasticity, which are key determinants of their role in controlling pyramidal cell excitability. Mechanisms underlying long-term changes at interneurone excitatory synapses, despite their importance, remain largely unknown. We use two-photon calcium imaging and whole-cell recordings to determine the Ca2+ signalling mechanisms linked specifically to group I metabotropic glutamate receptors (mGluR1alpha and mGluR5) and their role in hebbian long-term potentiation (LTP) in oriens/alveus (O/A) interneurones. We demonstrate that mGluR1alpha activation elicits dendritic Ca2+ signals resulting from Ca2+ influx via transient receptor potential (TRP) channels and Ca2+ release from intracellular stores. By contrast, mGluR5 activation produces dendritic Ca2+ transients mediated exclusively by intracellular Ca2+ release. Using Western blot analysis and immunocytochemistry, we show mGluR1alpha-specific extracellular signal-regulated kinase (ERK1/2) activation via Src in CA1 hippocampus and, in particular, in O/A interneurones. Moreover, we find that mGluR1alpha/TRP Ca2+ signals in interneurone dendrites are dependent on activation of the Src/ERK cascade. Finally, this mGluR1alpha-specific Ca2+ signalling controls LTP at interneurone synapses since blocking either TRP channels or Src/ERK and intracellular Ca2+ release prevents LTP induction. Thus, our findings uncover a novel molecular mechanism of interneurone-specific Ca2+ signalling, critical in regulating synaptic excitability in hippocampal networks.

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