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PubMed2003

Effects of leg movements on the synaptic activity of descending statocyst interneurons in crayfish, Procambarus clarkii.

Crustacean postural control is modulated by behavioral condition. In this study, we investigated how the responses of descending statocyst interneurons were affected during leg movements. Intracellular recording was made from an animal whose statoliths had been replaced with ferrite grains so that statocyst receptors could be activated by magnetic field stimulation. We identified 14 morphological types of statocyst-driven descending interneurons. Statocyst-driven descending interneurons always showed an excitatory response to statocyst stimulation on either ipsilateral or contralateral side to the axon. The response of each statocyst-driven descending interneuron to statocyst stimulation was differently modulated by leg movements in different conditions. During active leg movements, six statocyst-driven descending interneurons were activated regardless of whether a substrate was provided or not. In other two statocyst-driven descending interneurons, the excitatory input during leg movements was stronger when a substrate was provided than when it was not. One statocyst-driven descending interneuron received an excitatory input only during leg movements on a substrate, whereas another statocyst-driven descending interneuron did not receive any input during leg movements both on a substrate and in the air. These results suggest that the descending statocyst pathways are organized in parallel, each cell affected differently by behavioral conditions.

Action Potentials↗
PubMed2001

Monoamines and neuropeptides in antennal lobe interneurons of the desert locust, Schistocerca gregana: an immunocytochemical study.

As a first step towards unravelling some of the complexity of the signalling and modulatory mechanisms in the antennal lobe (AL) of the desert locust Schistocerca gregaria, I analysed the immunocytochemical identity of AL interneurons. Antibodies against serotonin, histamine, locustatachykinin, leucokinin and FMRFamide were used to reveal the morphology of interneurons ramifying in the AL. In addition, double-labelling experiments were performed in order to demonstrate colocalisation of GABA and locustatachykinin and to investigate the ramification patterns of immunolabelled interneurons and physiologically characterised olfactory projection neurons (PNs) injected with Lucifer yellow. Immunoreactivity to these antibodies revealed six different types of interneurons with different patterns of ramification within the glomerular neuropil: (1, 2) Centrifugal interneurons displaying serotonin immunoreactivity, which arborised extensively within the AL and extended varicose fibres into the microglomerular core where close associations with dendrites of AL PNs could be distinguished. (3) Histamine-immunoreactive centrifugal interneurons with arborisations in the protocerebrum and the dorsal non-glomerular regions of the AL and the lobus glomerulatus (LG). (4) Locustatachykinin-immunoreactive local interneurons, colocalising GABA, arborising throughout the AL and extending varicose fibres throughout the glomerular neuropil where close associations with dendrites of AL PNs could be distinguished. (5) Leucokinin-immunoreactive descending neurons connecting the protocerebrum, the AL, the LG and all ganglia of the ventral nerve cord. These neurons displayed sparse innervation of the AL and extended varicose fibres into the interglomerular space. (6) FMRF-amide-immunoreactive centrifugal interneurons, connecting the lateral protocerebrum with the AL and the LG, which arborised sparsely within these neuropils and displayed similar innervation of the microglomeruli as (1) and (2).

Animals↗
PubMed1995

Embryonic cortical neurons differentiate into various types of interneurons when heterotopically transplanted into the adult rat brain.

The adult cortex represents a heterogeneous mixture of different classes of pyramidal neurons and non-pyramidal interneurons. After grafting embryonic cortical anlage into the adult striatum, the present study investigated whether the development of different populations of interneurons in heterotopic cortical grafts is similar to the adult cortex. The presence of specific subpopulations of interneurons in grafts was assessed by immunocytochemistry using various antibodies against marker molecules for interneurons such as neuropeptides and calcium-binding proteins. These molecules are expressed to a different extent in specific subpopulations of cortical interneurons. Cortical primordia obtained on embryonic day 14 (E14) were stereotactically grafted into the center of the left striatum of adult recipient rats. After an 8-week differentiation period, host rats were perfusion fixed and immunocytochemistry was performed using antibodies against neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), somatostatin, parvalbumin and calbindin D-28k. Within the grafts, the number of immunopositive interneurons as well as the intensity of immunostaining for different marker molecules corresponded well with those of the adult cortex. In contrast, the expression pattern in the graft demonstrated clear differences when compared with the surrounding host striatum. The present study demonstrates, that at E14 at least some cells of the cortical anlage are primed to develop into different classes of interneurons independent of their normal environment and their regular synaptic connections. Thus, different interneuron progenitor cells survive transplantation and develop cell-specific morphological and cytochemical characteristics. Differentiation into various subpopulations of neurons may be a prerequisite for potential therapeutic approaches in humans.

Age Factors↗
PubMed2006

Spinal sympathetic interneurons: their identification and roles after spinal cord injury.

Primary afferent neurons rarely, if ever, synapse on the sympathetic preganglionic neurons that regulate the cardiovascular system, nor do sympathetic preganglionic neurons normally exhibit spontaneous activity in the absence of excitatory inputs. Therefore, after serious spinal cord injury "spinal sympathetic interneurons" provide the sole excitatory and inhibitory inputs to sympathetic preganglionic neurons. Few studies have addressed the anatomy and physiology of spinal sympathetic interneurons, to a great extent because they are difficult to identify. Therefore, this chapter begins with descriptions of both neurophysiological and neuroanatomical criteria for identifying spinal sympathetic interneurons, and it discusses the advantages and disadvantages of each. Spinal sympathetic interneurons also have been little studied because their importance in intact animals has been unknown, whereas the roles of direct projections from the brain to sympathetic preganglionic neurons are better known. This chapter presents evidence that spinal sympathetic interneurons play only a minor role in sympathetic regulation when the spinal cord is intact. However, they play an important role after spinal cord injury, both in generating ongoing activity in sympathetic nerves and in mediating segmental and intersegmental sympathetic reflexes. The spinal sympathetic interneurons that most directly influence the activity of sympathetic preganglionic neurons after spinal cord injury are located close to their associated sympathetic preganglionic neurons, and the inputs from distant segments that mediate multisegmental reflexes are relayed to sympathetic preganglionic neurons multisynaptically via spinal sympathetic interneurons. Finally, spinal sympathetic interneurons are more likely to be excited and less likely to be inhibited by both noxious and innocuous somatic stimuli after chronic spinal transection. The onset of this hyperexcitability corresponds to morphological changes in both sympathetic preganglionic neurons and primary afferents, and it may reflect the pathophysiological processes that lead to autonomic dysreflexia and the hypertensive crises that may occur with it in people after chronic spinal injury.

Animals↗
PubMed1993

Interactions between pathways controlling posture and gait at the level of spinal interneurones in the cat.

The properties of three interneuronal populations controlling posture and locomotion are briefly reviewed. These are interneurones mediating reciprocal inhibition of antagonistic muscles and interneurones in pathways from secondary muscle spindle afferents to ipsilateral and contralateral motoneurones, respectively. It will be shown that these interneurones subserve a variety of movements, with functionally specialized subpopulations being selected under different conditions. Mechanisms for gating the activity of these neurones appear to be specific for each of them but to act in concert. Interneurones which are active during locomotion and postural reactions are distributed over many segments of the spinal cord and over several of Rexed's laminae, both in the intermediate zone and in the ventral horn (Berkinblit et al., 1978; Bayev et al., 1979; Schor et al., 1986; Yates et al., 1989). The location of neurones discharging during neck and labyrinthine reflexes is illustrated in Fig. 1A and B but indications that neurones with an even wider distribution contribute to locomotion, scratching and the related postural reactions have been provided by neuronal markers which preferentially label active neurones (WGA-HRP; see Noga et al., 1987) or neurones with active genetic transcription (c-fos; I. Barajon, personal communication; Dai et al., 1991). Such a wide distribution indicates a high degree of non-homogeneity, since neurones of different functional types are usually located in different laminae. It has been demonstrated that some of these neurones may be particularly important for setting up the rhythm of muscle contractions specific for different gaits or scratching, as part of their "pattern generators" (see, e.g., Grillner, 1981). Other neurones may be primarily involved in initiation of these movements or in postural adjustments combined with them. A considerable proportion of neurones mediating these movements are nevertheless likely to be used not in one particular type of movement but in a variety of movements, and contribute to postural reactions and locomotion as well as to various segmental reflexes and centrally initiated movements; they are likely to operate as last order (premotor) interneurones of several spinal pathways to motoneurones. One of the indications that this is the case is the overlap between the areas of location of interneurones active during postural reactions, locomotion, or scratching and the areas of location of premotor interneurones (Fig. 1C,D). The latter were labelled by loading motoneurones with WGA-HRP and by its subsequent retrograde transneuronal transport (see Harrison et al., 1986).(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed2003

Intracerebroventricular kainic acid administration to neonatal rats alters interneuron development in the hippocampus.

The effects of neonatal exposure to excitotoxins on the development of interneurons have not been well characterized, but may be relevant to the pathogenesis of neuropsychiatric disorders. In this study, the excitotoxin, kainic acid (KA) was administered to rats at postnatal day 7 (P7) by intracerebroventricular (i.c.v.) infusion. At P14, P25, P40 and P60, Nissl staining and immunohistochemical studies with the interneuron markers, glutamic acid decarboxylase (GAD-67), calbindin-D28k (CB) and parvalbumin (PV) were performed in the hippocampus. In control animals, the total number of interneurons, as well as the number of interneurons stained with GAD-67, CB and PV, was nearly constant from P14 through P60. In KA-treated rats, Nissl staining, GAD-67 staining, and CB staining revealed a progressive decline in the overall number of interneurons in the CA1 and CA3 subfields from P14 to P60. In contrast, PV staining in KA-treated rats showed initial decreases in the number of interneurons in the CA1 and CA3 subfields at P14 followed by increases that approached control levels by P60. These results suggest that, in general, early exposure to the excitotoxin KA decreases the number of hippocampal interneurons, but has a more variable effect on the specific population of interneurons labeled by PV. The functional impact of these changes may be relevant to the pathogenesis of neuropsychiatric disorders, such as schizophrenia.

Aging↗
PubMed2000

Cell death of spinal interneurones.

The occurrence of neuronal death during development is well documented for some neuronal populations, such as motoneurones and dorsal root ganglion cells, whose connecting pathways are clearly defined. Cell survival is thought to be regulated largely by target and input connections, a process that serves to match the size of synaptically linked neuronal populations. Far less is known about interneurones. It is assumed that most interneurone populations are excluded from this process because their connections are more diffuse. Recent studies on the rat spinal cord have indicated that interneurone death does occur, both naturally during development and induced following peripheral nerve injury. Here the evidence for spinal interneurone death is reviewed and the factors influencing it are discussed. There are many functional types of interneurones in the spinal cord that may differ in vulnerability to cell death, but it is concluded that for most spinal interneurones the traditional view of target regulation is unlikely. Instead it is proposed that developmental interneurone death in the spinal cord forms part of a plastic response to altered sensory activation rather than a size-matching exercise. There is also emerging evidence that interneurone death may play a more direct role in some neurodegenerative diseases than hitherto considered.

Animals↗
PubMed2002

Projection neurons and interneurons in the lateral geniculate nucleus undergo distinct forms of degeneration ranging from retrograde and transsynaptic apoptosis to transient atrophy after cortical ablation in rat.

The cytological responses of thalamic interneurons to selective degeneration of thalamocortical projection neurons after cortical damage in the adult brain are poorly understood. We used a unilateral neocortical lesion model (occipital cortex ablation) in the adult rat to test the hypothesis that interneurons and projection neurons in the lateral geniculate nucleus undergo distinct forms of degeneration. In situ nuclear DNA fragmentation in neurons in the lateral geniculate occurs maximally at 7 days postlesion. Geniculocortical projection neurons that are identified by the retrograde tracer Fluorogold die primarily with a morphology of endstage apoptosis prominent at 7 days postlesion. In contrast, interneurons, identified by their particular nuclear ultrastructure and by glutamic acid decarboxylase immunoreactivity, undergo an atrophic vacuolar pathology starting early during the period of projection neuron death and peaking after the projection neuron death is complete. This degeneration of interneurons is transient, because these neurons exhibit structural recovery and their numbers are not changed significantly postlesion. A rare subset of interneurons (less than one in 100 interneurons and less than one in 100 apoptotic cells) undergoes apoptosis concurrently with the projection neurons. We conclude that different types of neurons within the same thalamic nucleus respond differently to focal cortical target deprivation. Unlike the apoptosis-prone projection neurons, most interneurons undergo transient transsynaptic atrophy and recovery rather than cell death. Nevertheless, a small subset of lateral geniculate interneurons undergoes transsynaptic apoptosis in response to projection neuron apoptosis. The pathological responses of thalamic neurons to cortical trauma vary depending on cell type.

Animals↗
PubMed1997

Nicotinic receptor-mediated responses in relay cells and interneurons in the rat lateral geniculate nucleus.

We used the in vitro whole-cell recording technique to study the nicotinic responses of relay cells and interneurons in the adult rat dorsal lateral geniculate nucleus, the thalamic nucleus that conveys visual signals from the retina to the cortex. These geniculate relay cells and interneurons were identified by their physiological and morphological properties. We found that, in the presence of a muscarinic antagonist, atropine, acetylcholine induced a depolarization in relay cells. A similar depolarization was induced by application of nicotine. These depolarizations were completely blocked by a nicotinic antagonist, hexamethonium, but were little affected by bath solution that contained tetrodotoxin and/or low calcium concentration to block synaptic transmission. This suggests that the depolarization is mediated directly by nicotinic receptors in relay cells. Application of nicotine also induced a depolarization in geniculate interneurons. The interneurons continued to exhibit a response to nicotine in the presence of synaptic blockade, although the time-course of the response was altered. The nicotinic responses in relay cells and interneurons shared many similar properties. Both exhibited desensitization, although this characteristic was much more pronounced in the interneurons. In both cell types, the nicotinic response activated a relatively linear conductance with a slight inward rectification. The reversal potential for the conductance was about - 33 mV, which is consistent with a permeability to sodium and potassium ions. The reversal potential shifted negatively by 5-6 mV when the bath solution contained low calcium, which further suggests a permeability to calcium ions. Our results indicate that nicotinic receptors are present in both geniculate relay cells and interneurons. The nicotinic depolarization in relay cells may serve to enhance transmission of visual signals through the lateral geniculate nucleus as well as to contribute to a voltage-dependent shift in the response mode of geniculate relay cells from burst to tonic (single-spike) firing. The nicotinic depolarization in interneurons may provide an explanation for reports that activation of the cholinergic system can enhance inhibitory tuning in the lateral geniculate nucleus.

Acetylcholine↗
PubMed1998

Identification of lamina V and VII interneurons presynaptic to adrenal sympathetic preganglionic neurons in rats using a recombinant herpes simplex virus type 1.

Although indirect evidence suggests that the control of sympathetic preganglionic neurons is mediated to a great extent through interneurons, little is known about the location, morphology or neurotransmitter phenotype of such interneurons. This limitation seriously impedes our understanding of spinal synaptic circuits crucial to control of arterial pressure and other visceral functions. We used a highly neurotropic, minimally cytopathic recombinant herpes simplex virus type-1 to study spinal "sympathetic" interneurons labelled by trans-synaptic transport of the virus from the adrenal gland in rats. Approximately 120-320 infected neurons/rat were identified by immunocytochemical detection of the viral antigen. We distinguished between virus-infected preganglionic neurons and infected interneurons by (i) their location within the spinal laminae, (ii) their size and shape and (iii) the presence or absence of immunoreactivity for the acetylcholine-synthesizing enzyme, choline acetyltransferase, a marker of sympathetic preganglionic neurons. Virus-labelled sympathetic preganglionic neurons were found within the known spinal preganglionic nuclei. Non-cholinergic, virus-labelled neurons were located throughout lamina VII and in the ventral portion of lamina V. These putative interneurons were found in the major spinal preganglionic nuclei, usually intermingled with the preganglionic neurons. Sometimes, they were located in clusters separate from the preganglionic neurons. The interneurons were approximately 15 microm in diameter, smaller than the average preganglionic neuron (diameter=25 microm), and had a few fine processes emanating from them. These non-cholinergic interneurons constituted approximately one-half of the population of virus-infected neurons. In summary, with the use of a recombinant herpes simplex virus, we identified a large number of non-cholinergic interneurons close to, or intermingled with, adrenal sympathetic preganglionic neurons. The neurotransmitter phenotype of these neurons remains to be determined but they likely integrate much of the supraspinal and primary afferent inputs to spinal preganglionic neurons that control arterial pressure and other visceral functions.

Adrenal Glands↗
PubMed1997

Simulation of gamma rhythms in networks of interneurons and pyramidal cells.

Networks of hippocampal interneurons, with pyramidal neurons pharmacologically disconnected, can generate gamma-frequency (20 Hz and above) oscillations. Experiments and models have shown how the network frequency depends on excitation of the interneurons, and on the parameters of GABAA-mediated IPSCs between the interneurons (conductance and time course). Here we use network simulations to investigate how pyramidal cells, connected to the interneurons and to each other through AMPA-type and/or NMDA-type glutamate receptors, might modify the interneuron network oscillation. With or without AMPA-receptor mediated excitation of the interneurons, the pyramidal cells and interneurons fired in phase during the gamma oscillation. Synaptic excitation of the interneurons by pyramidal cells caused them to fire spike doublets or short bursts at gamma frequencies, thereby slowing the population rhythm. Rhythmic synchronized IPSPs allowed the pyramidal cells to encode their mean excitation by their phase of firing relative to the population waves. Recurrent excitation between the pyramidal cells could modify the phase of firing relative to the population waves. Our model suggests that pools of synaptically interconnected inhibitory cells are sufficient to produce gamma frequency rhythms, but the network behavior can be modified by participation of pyramidal cells.

Electroencephalography↗
PubMed2005

Asynchronous GABA release generates long-lasting inhibition at a hippocampal interneuron-principal neuron synapse.

Hippocampal GABAergic interneurons show diverse molecular and morphological properties. The functional significance of this diversity for information processing is poorly understood. Here we show that cholecystokinin (CCK)-expressing interneurons in rat dentate gyrus release GABA in a highly asynchronous manner, in contrast to parvalbumin (PV) interneurons. With a gamma-frequency burst of ten action potentials, the ratio of asynchronous to synchronous release is 3:1 in CCK interneurons but is 1:5 in parvalbumin interneurons. N-type channels trigger synchronous and asynchronous release in CCK interneuron synapses, whereas P/Q-type Ca(2+) channels mediate release at PV interneuron synapses. Effects of Ca(2+) chelators suggest that both a long-lasting presynaptic Ca(2+) transient and a large distance between Ca(2+) source and sensor of exocytosis contribute to the higher ratio of asynchronous to synchronous release in CCK interneuron synapses. Asynchronous release occurs at physiological temperature and with behaviorally relevant stimulation patterns, thus generating long-lasting inhibition in the brain.

Action Potentials↗
PubMed1999

Expression of TrkB and TrkC but not BDNF mRNA in neurochemically identified interneurons in rat visual cortex in vivo and in organotypic cultures.

The mammalian visual cortex contains morphologically diverse populations of interneurons whose neurochemical properties are believed to be regulated by neurotrophic factors. This requires the expression of neurotrophin receptors. We have analysed whether brain-derived neurotrophic factor (BDNF), its receptor trkB and the NT-3 receptor trkC are expressed in interneurons of rat visual cortex in vivo, and in organotypic visual cortex cultures, paying particular attention to the subsets of neuropeptidergic neurons. In situ hybridization in combination with immunofluorescence for calcium-binding proteins and neuropeptides revealed that BDNF is not expressed in interneurons in vivo or in vitro. For the neurotrophin receptors we found in vivo at postnatal day 70 (P70) that approximately 80% of the parvalbumin-immunoreactive (-ir), but only 50% of the intensely calbindin-ir, and only 20% of the calretinin-ir neurons express trkB. Double labelling with neuropeptides revealed that approximately 50% of the neuropeptide Y-ir and approximately 50% of the somatostatin-ir neurons express trkB in a laminar-specific way. Only 25% of the vasoactive intestinal polypeptide (VIP)-ir neurons coexpress trkB. The coexpression of neuropeptide Y with trkB, but not with BDNF or trkC, was confirmed with a double in situ hybridization. In contrast, the percentages differed in the immature cortex; at P14 70% of the NPY-ir neurons and 46% of the calretinin-ir neurons revealed trkB expression, while the ratio for calbindin-ir cells was fairly constant (59%). From the interneuron populations studied, only 12% of the parvalbumin-ir neurons expressed trkC. A triple labelling revealed that some neurons coexpressed both trk mRNAs, while others had only trkC. The analysis of interneurons in organotypic cultures yielded very similar results. The results indicate that trkB ligands synthesized by pyramidal neurons influence neuropeptide or calcium-binding protein expression in a paracrine or transsynaptic manner. However, in contrast to current belief, in the adult only about half of all interneurons appear responsive to trkB ligands. Although the proportion is higher in the immature cortex, not all of the interneurons appear neurotrophin-receptive. With regard to the presence or absence of neurotrophin receptors, the molecular heterogeneity of GABAergic interneurons in the visual cortex is higher than currently assumed, and the responsiveness to neurotrophins changes with development in a cell type-specific way.

Animals↗
PubMed1999

Synchronization of GABAergic interneuronal networks during seizure-like activity in the rat horizontal hippocampal slice.

We studied the contribution of GABAergic (gamma-aminobutyric acid) neurotransmission to epileptiform activity using the horizontal hippocampal rat brain slice. Seizure-like (ictal) activity was evoked in the CA1 area by applying high-frequency trains (80 Hz for 2 s) to the Schaffer collaterals. Whole-cell recordings from stratum oriens-alveus interneurons revealed burst firing with superimposed high-frequency spiking which was synchronous with field events and pyramidal cell firing during ictal activity. On the other hand, interictal interneuronal bursts were synchronous with large-amplitude inhibitory postsynaptic potentials (IPSPs) in pyramidal cells. Excitatory and inhibitory postsynaptic potentials were simultaneously received by pyramidal neurons during the ictal afterdischarge, and were synchronous with interneuronal bursting and field potential ictal events. The GABAA receptor antagonist bicuculline greatly reduced the duration of the ictal activity in the CA1 layer, and evoked rhythmic interictal synchronous bursting of interneurons and pyramidal cells. With intact GABAergic transmission, interictal field potential events were synchronous with large amplitude IPSPs (9.8 +/- 2.4 mV) in CA1 pyramidal cells, and with interneuronal bursting. Simultaneous dual recordings revealed synchronous IPSPs received by widely separated pyramidal neurons during ictal and interictal periods, indicative of widespread interneuronal firing synchrony throughout the hippocampus. CA3 pyramidal neurons fired in synchrony with interictal field potential events recorded in the CA1 layer, and glutamate receptor antagonists abolished interictal interneuronal firing and synchronous large amplitude IPSPs received by CA1 pyramidal cells. These observations provide evidence that the interneuronal network may be entrained in hyperexcitable states by GABAergic and glutamatergic mechanisms.

2-Amino-5-phosphonovalerate↗
PubMed2003

Contact-associated neurite outgrowth and branching of immature cortical interneurons.

When juvenile interneurons arrive at the cortical environment following tangential migration, they are faced with the task of positioning themselves in cortical space in preparation for local circuit wiring. This includes integration into different cortical layers and cessation of migration at various positions to ensure adequate coverage. Little is known about the signals or mechanisms that initiate a conversion from the migratory phenotype to the arborization phenotype. This study looks at the immediate changes in interneuron morphology after culturing for 24 h in a three-dimensional collagen gel. Immature interneurons taken from different stages of corticogenesis showed increased neurite branching and outgrowth after interneuronal contacts were made. These responses were suppressed in the presence of Slit and brain-derived neurotrophic factor (BDNF) if the interneurons were sourced from early to mid-stages of corticogenesis. However, interneurons taken from the late period of corticogenesis responded to Slit and BDNF by increasing branching and neurite outgrowth. These results suggest an initial interneuronal cell contact as a stimulus for propagating neuronal arborization that may lead to the formation of inhibitory neuronal circuits. In addition, we have identified the late corticogenetic period when interneurons are most sensitive to the neurite promoting effects of Slit and BDNF.

Animals↗
PubMed2001

Agent-selective effects of volatile anesthetics on GABAA receptor-mediated synaptic inhibition in hippocampal interneurons.

BACKGROUND: A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal cells in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role for the maintenance of anesthesia. The aim of this study was to compare effects produced by volatile anesthetics on inhibitory postsynaptic currents (IPSCs) of rat hippocampal interneurons. METHODS: Pharmacologically isolated gamma-aminobutyric acid type A (GABAA) receptor-mediated IPSCs were recorded with whole cell patch-clamp techniques in visually identified interneurons of rat hippocampal slices. Neurons located in the stratum radiatum-lacunosum moleculare of the CA1 region were studied. The effects of clinically relevant concentrations (1.0 rat minimum alveolar concentration) of halothane, enflurane, isoflurane, and sevoflurane were compared on kinetics of both stimulus-evoked and spontaneous GABAA receptor-mediated IPSCs in interneurons. RESULTS: Halothane (1.2 vol% approximately 0.35 mm), enflurane (2.2 vol% approximately 0.60 mm), isoflurane (1.4 vol% approximately 0.50 mm), and sevoflurane (2.7 vol% approximately 0.40 mm) preferentially depressed evoked IPSC amplitudes to 79.8 +/- 9.3% of control (n = 5), 38.2 +/- 8.6% (n = 6), 52.4 +/- 8.4% (n = 5), and 46.1 +/- 16.0% (n = 8), respectively. In addition, all anesthetics differentially prolonged the decay time constant of evoked IPSCs to 290.1 +/- 33.2% of control, 423.6 +/- 47.1, 277.0 +/- 32.2, and 529 +/- 48.5%, respectively. The frequencies of spontaneous IPSCs were increased by all anesthetics (twofold to threefold). Thus, the total negative charge transfer mediated by GABAA receptors between synaptically connected interneurons was enhanced by all anesthetics. CONCLUSIONS: Volatile anesthetics differentially enhanced GABAA receptor-mediated synaptic inhibition in rat hippocampal interneurons, suggesting that hippocampal interneuron circuits are depressed by these anesthetics in an agent-specific manner.

Anesthetics, Inhalation↗
PubMed2005

Age-dependent alterations of striatal calretinin interneuron density in a genetic animal model of primary paroxysmal dystonia.

Various types of hereditary dystonia are regarded as a basal ganglia disorder, but the underlying mechanisms are still unknown. In the dt hamster, a genetic animal model of age-dependent paroxysmal dystonia, recent studies demonstrated a reduced density of striatal parvalbumin-immunoreactive (PV) GABAergic interneurons at an age of maximum severity of dystonia in comparison with age-matched nondystonic controls. So far, alterations of other types of striatal interneurons in dt hamsters cannot be excluded. Therefore, we determined the density of calretinin-immunoreactive (CR) interneurons in the dt mutant at an age of maximum severity and after spontaneous remission of dystonia in comparison with age-matched nondystonic controls using an image analysis system and a stereologic counting method in a blinded fashion. At an age of maximum severity of dystonia, CR interneuron density was significantly lower in dt hamsters in comparison with controls (-20%), whereas no significant differences between the animal groups could be detected after spontaneous remission of dystonia. The comparison of CR interneuron density between young hamsters with those at an age of > 90 days revealed a significant ontogenetic decrease of CR interneurons in both animal groups (dt hamsters: -38%, controls: -54%). These results demonstrate that alterations of striatal interneuron density in dt mutants are not restricted to PV ones. A deficit of CR interneurons that coexpress GABA may contribute to previous findings of disinhibition of striatal projection neurons in the dt mutant at an age of maximum expression of dystonia.

Age Factors↗
PubMed1997

Interneurons in the hippocampal dentate gyrus: an in vivo intracellular study.

Interneurons in the dentate area were characterized physiologically and filled with biocytin in urethane-anaesthetized rats. On the basis of axonal targets the following groups could be distinguished. (i) Large multipolar interneurons with spiny dendrites in the deep hilar region densely innervated the outer molecular layer and contacted both granule cells and parvalbumin-positive neurons (hilar interneuron with perforant pathway-associated axon terminals; HIPP cells). (ii) A pyramidal-shaped neuron with a cell body located in the subgranular layer innervated mostly the inner molecular layer and the granule cell layer (hilar interneuron with commissural-associational pathway-associated axon terminals; HICAP cell). It contacted both granule cells and interneurons. Axon collaterals of HIPP and HICAP neurons covered virtually the entire septo-temporal extent of the dorsal dentate gyrus. (iii) Calbindin-immunoreactive neurons with horizontal dendrites in stratum oriens of the CA3c region gave rise to a rich axon arbor in strata oriens, pyramidale and radiatum and innervated almost the entire extent of the dorsal hippocampus, with some collaterals entering the subicular area (putative trilaminar cell). (iv) Hilar basket cells innervated mostly the granule cell layer and to some extent the inner molecular layer and the CA3c pyramidal layer. HIPP and trilaminar interneurons could be antidromically activated by stimulation of the fimbria. Only the HICAP cells could be monosynaptically discharged by the perforant path input. All interneurons examined showed phase-locked activity to the extracellularly recorded theta/gamma oscillations or to irregular dentate electroencephalogram spikes. These observations indicate that the interconnected interneuronal system plays a critical role in coordinating population of the dentate gyrus and Ammon's hom.

Animals↗