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ABSTRACT: The neuronal Ca2+-sensor protein VILIP-1, known to affect clathrin-dependent receptor trafficking, has been shown to interact with the cytoplasmic loop of the α4-subunit of the α4β2 nicotinic acetylcholine receptor (nAChR), which is the most abundant nAChR subtype with high-affinity for nicotine in the brain. The α4β2 nAChR is crucial for nicotine addiction and the beneficial effects of nicotine on cognition. Its dysfunction has been implicated in frontal lobe epilepsy, Alzheimer's disease and schizophrenia. Here we report that overexpression of VILIP-1 enhances ACh responsiveness, whereas siRNA against VILIP-1 reduces α4β2 nAChR currents of hippocampal neurons. The underlying molecular mechanism likely involves enhanced constitutive exocytosis of α4β2 nAChRs mediated by VILIP-1. The two interaction partners co-localize in a Ca2+-dependent manner with syntaxin-6, a Golgi-SNARE protein involved in trans-Golgi membrane trafficking. Thus, we speculate that regulation of VILIP-1-expression might modulate surface expression of ligand-gated ion channels, such as the α4β2 nAChRs, possibly comprising a novel form of physiological up-regulation of ligand-gated ion channels.
Molecular and Cellular Neuroscience - MOL CELL NEUROSCI. 01/2009; 40(2):280-292.
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ABSTRACT: The neuronal Ca2+-sensor protein VILIP-1, known to affect clathrin-dependent receptor trafficking, has been shown to interact with the cytoplasmic loop of the alpha4-subunit of the alpha4beta2 nicotinic acetylcholine receptor (nAChR), which is the most abundant nAChR subtype with high-affinity for nicotine in the brain. The alpha4beta2 nAChR is crucial for nicotine addiction and the beneficial effects of nicotine on cognition. Its dysfunction has been implicated in frontal lobe epilepsy, Alzheimer's disease and schizophrenia. Here we report that overexpression of VILIP-1 enhances ACh responsiveness, whereas siRNA against VILIP-1 reduces alpha4beta2 nAChR currents of hippocampal neurons. The underlying molecular mechanism likely involves enhanced constitutive exocytosis of alpha4beta2 nAChRs mediated by VILIP-1. The two interaction partners co-localize in a Ca2+-dependent manner with syntaxin-6, a Golgi-SNARE protein involved in trans-Golgi membrane trafficking. Thus, we speculate that regulation of VILIP-1-expression might modulate surface expression of ligand-gated ion channels, such as the alpha4beta2 nAChRs, possibly comprising a novel form of physiological up-regulation of ligand-gated ion channels.
Molecular and Cellular Neuroscience 12/2008; 40(2):280-92. · 3.66 Impact Factor
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06/2006: pages 65-78;
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ABSTRACT: Retrogradely labeled cells in superficial and deep layers of the entorhinal cortex (EC) were analyzed following application of the fluorescent tracer rhodamine-dextran-amine in different sites of the hippocampal formation in a slice preparation. The results demonstrate a strong projection from layer IV/V to the dentate gyrus, that is in slices significantly stronger than that from layer II. In deep layers a large number of multipolar cells were found which were only labeled by dye application to the subiculum. Patch-clamp recordings from these cells revealed intrinsic low threshold membrane potential oscillations, suggesting their possible contribution to oscillatory network activity of the EC and subiculum.
Brain Research 07/2001; 905(1-2):224-31. · 2.73 Impact Factor
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ABSTRACT: Medial entorhinal cortex (EC) deep layer neurons projecting to the dentate gyrus (DG) were studied. Neurons, retrogradely-labelled with rhodamine-dextran-amine were characterized electrophysiologically with the patch clamp technique and finally labelled with biocytin. Pyramidal and nonpyramidal neurons form projections from the deep layers of the EC to the molecular layer of the DG. In addition, both classes of projection neurons send ascending axon collaterals to the superficial layers of the EC. Both classes of neurons were characterized physiologically by regular action potential firing upon depolarizing current injection. While a substantial number of pyramidal projection cells showed intrinsic membrane potential oscillations, none of the studied nonpyramidal cells exhibited oscillations. Despite the morphological similarity of bipolar and multipolar cells to those of GABAergic interneurons in the EC, their electrophysiological characteristics were similar to those of principal neurons and immunocytochemistry for GABA was negative. We conclude, that neurons of the deep layers of the medial EC projecting to the DG may function as both local circuit and projecting neurons thereby contributing to synchronization between deep layers of the EC, superficial layers of the EC and the DG.
European Journal of Neuroscience 02/2001; 13(2):413-20. · 3.63 Impact Factor
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ABSTRACT: Schizophrenia is considered to be associated with an abnormal functioning of the hippocampal output. The high clinical potency of antipsychotics that act as antagonists at dopamine (DA) receptors indicate a hyperfunction of the dopaminergic system. The subiculum obtains information from area CA1 and the entorhinal cortex and represents the major output region of the hippocampal complex. To clarify whether an enhanced dopaminergic activity alters the hippocampal output, the effect of DA on alveus- and perforant path-evoked excitatory postsynaptic currents (EPSCs) in subicular neurons was examined using conventional intracellular and whole cell voltage-clamp recordings. Dopamine (100 microM) depressed alveus-elicited (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated EPSCs to 56 +/- 8% of control while perforant path-evoked EPSCs were attenuated to only 76 +/- 7% of control. Dopamine had no effect on the EPSC kinetics. Dopamine reduced the frequency of spontaneous miniature EPSCs without affecting their amplitudes. The sensitivity of subicular neurons to the glutamate receptor agonist (S)-alpha-amino-3-hydoxy-5-methyl-4-isoxazolepropionic acid was unchanged by DA pretreatment, excluding a postsynaptic mechanism for the observed reduction of excitatory synaptic transmission. The effect of DA on evoked EPSCs was mimicked by the D1 receptor agonist SFK 38393 and partially antagonized by the D1 receptor antagonist SCH 23390. While the D2 receptor agonist quinelorane failed to reduce the EPSCs, the D2 receptor antagonist sulpiride did not block the action of DA. The results indicate that DA strongly depresses the hippocampal and the entorhinal excitatory input onto subicular neurons by decreasing the glutamate release following activation of presynaptic D1-like DA receptors.
Journal of Neurophysiology 08/2000; 84(1):112-9. · 3.32 Impact Factor
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ABSTRACT: There are multiple connections from the entorhinal cortex (EC) to the hippocampus that carry the information from the EC to the hippocampus. Layer II cells of the medial EC innervating the dentate gyrus (DG)-molecular layer possess K(+)-outward currents and inward rectifier currents that are potentially modulated by changes in intracellular second messengers. Layer II cells responded to synaptic stimulation with a rather flat input-output curve, and much stronger stimuli are required to generate action potentials in these neurons than in EC layer III cells. During repetitive stimulation at frequencies of 10 Hz and more, EC layer II cells respond with increased likelihood to generate action potentials. Two different NMDA conductances can be demonstrated in these neurons. A slow, less Mg, less voltage-dependent component is responsible for the transient depolarization between the fast and slow IPSP. A second group of neurons also projects to the DG. These are either pyramidal or nonpyramidal cells in the deep layers of the EC. At least part of these neurons also possess rhythmogenic properties. In contrast to layer II cells, layer III neurons have a steep input-output curve and show during repetitive synaptic activation a tendency to repolarize and to display long-lasting inhibitions dependent on GABAB-, atropine-, and naloxone-sensitive components. As a consequence, they are readily activated during low frequency stimulation, but project only a few action potentials to area CA1 initially during higher (more than 10 Hz) frequency synaptic stimulation.
Annals of the New York Academy of Sciences 07/2000; 911:112-26. · 3.15 Impact Factor
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ABSTRACT: The entorhinal cortex (EC) is a major gateway for sensory information into the hippocampus and receives a cholinergic input from the forebrain. Therefore, we studied muscarinic effects on excitability and intracellular Ca2+ signalling in layer II stellate and layer III pyramidal projection neurons of the EC. In both classes of neurons, local pressure-pulse application of carbachol (1 mM) caused small, atropine-sensitive membrane depolarizations that were not accompanied by any detectable changes in [Ca2+]i. At a higher concentration (10 mM), carbachol induced a larger membrane depolarization associated with synaptic oscillations and epileptiform activity in both classes of neurons. In contrast to the intrinsic theta rhythm in stellate cells with one dominant peak frequency at approximately 7 Hz, the synaptically mediated oscillation induced by carbachol showed three characteristic peaks in the theta and gamma frequency range at approximately 11, 23 and 40 Hz. Although carbachol-induced epileptiform activity was associated with increases in intracellular free Ca2+ in both layer II and III cells, the observed [Ca2+]i accumulation was significantly larger in layer III than in layer II cells. Responses to intracellular current injections showed differences in Ca2+ accumulation in layer II and III cells at the same membrane potentials, suggesting a dominant expression of low- and high-voltage-activated Ca2+ channels in these layer II and III cells, respectively. In conclusion, we present evidence for significant differences in the [Ca2+]i regulation between layer II stellate and layer III pyramidal cells of the medial EC.
European Journal of Neuroscience 11/1999; 11(10):3626-36. · 3.63 Impact Factor
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ABSTRACT: The cholinergic system is critically involved in synaptic models of learning and memory by enhancing dendritic [Ca(2+)](i) signals. Diffuse cholinergic innervation suggests subcellular modulation of membrane currents and Ca(2+) signals. Here we use ion-selective microelectrodes to study spread of carbachol (CCh) after focal application into brain slice and subcellular muscarinic modulation of synaptic responses in CA1 pyramidal neurons. Proximal application of CCh rapidly blocked the somatic slow afterhyperpolarization (sAHP) following repetitive stimulation. In contrast, the time course of potentiation of the slow tetanic depolarization (STD) during synaptic input was slower and followed the time course of spread of CCh to the dendritic tree. With distal application, augmentation of the somatic STD and of dendritic Ca(2+) responses followed spread of CCh to the entire apical dendritic tree, whereas the sAHP was blocked only after spread of CCh to the proximal dendritic segment. In dendritic recordings, CCh blocked a small sAHP, augmented the STD, and rather reduced dendritic action potentials. Augmentation of dendritic Ca(2+) signals was highly correlated to augmentation of the STD. The NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) blocked approximately 55% of the STD in control and during CCh application. In conclusion, muscarinic suppression of the proximal sAHP can augment firing and thereby Ca(2+) responses. Dendritic augmentation of the STD by blockade of the sAHP and direct enhancement of N-methyl-D-aspartate (NMDA) receptor-mediated currents potentiates Ca(2+) signals even when firing is not affected due to suprathreshold input. In this way, subcellular muscarinic modulation may contribute to parallel information processing and storage by dendritic synapses of CA1 pyramidal neurons.
Journal of Neurophysiology 11/1999; 82(4):1909-15. · 3.32 Impact Factor
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ABSTRACT: 1. The entorhinal cortex (EC), main input structure to the hippocampus, gets innervated by serotonergic terminals from the raphe nuclei and expresses 5-HT-receptors at high density. Using extra- and intracellular recording techniques we here investigated the effects of serotonin on population and cellular responses within the EC. 2. Stimulation in the lateral entorhinal cortex resulted in complex field potential responses in the superficial EC. The potentials are composed of an early antidromic and a late orthodromic component reflecting the efferent and afferent circuitry. 3. Serotonin (5-HT) reduced synaptic potentials of the stimulus evoked extracellular field potential at all concentrations tested (0. 1 - 100 microM; 59%-depression by 10 microM serotonin), while the antidromic response was not significantly changed by up to 50 microM 5-HT. Depression of field potential responses by serotonin was associated with a significant increase in paired-pulse facilitation from 1.15 to 1.88. 4. The effects of serotonin on field potential responses were mimicked by 5-HT1A-receptor agonists (8-OH-DPAT, 5-CT) and partially prevented by the 5-HT1A-receptor antagonist (S-UH-301). Moreover, the 5-HT1A-receptor antagonist WAY100635 reduced the effect of 5-CT. 5. Fenfluramine, a serotonin releaser, mimics the effects of serotonin on stimulus-evoked field potential responses, indicating that synaptically released serotonin can produce the changes in reactivity to afferent stimulation. 6. Depression of isolated AMPA-receptor mediated EPSCs by serotonin as well as fenfluramine was associated with an increase in paired pulse facilitation, indicating a presynaptic locus of action. 7. We conclude that physiological concentrations of serotonin potently suppresses excitatory synaptic transmission in the superficial entorhinal cortex by a presynaptic mechanism.
British Journal of Pharmacology 10/1999; 128(1):248-54. · 4.41 Impact Factor
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ABSTRACT: L-Glutamic acid (Glu) is a key excitatory transmitter in the central nervous system. Excessive amounts of Glu are highly toxic to neurons and particularly the entorhinal cortex (EC) exhibits a remarkable loss of cells in the superficial layers in acute brain injury. The accumulation of Glu is limited by a family of high-affinity Glu transporters. Using extracellular potential recordings in rat brain slices we tested whether application of the Glu uptake blockers dihydrokainate and L-trans-pyrrolidine-2,4-dicarboxylate (L-trans-2,4-PDC) affect stimulus-induced field potentials (FPs) in superficial layer III and deep layer V of the medial EC. We found that a high concentration (400 microM) of the uptake blockers significantly reduces stimulus-induced FPs in both layers. At lower concentration (200 microM), only dihydrokainate is efficient. The data show that Glu uptake is involved in the control of extracellular Glu levels during synaptic excitation of layers III and V of the medial EC.
Neuroscience Letters 02/1999; 259(2):103-6. · 2.11 Impact Factor
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ABSTRACT: 1. The axonal plexus of most hippocampal interneurons is restricted to certain strata within the target region. This lamination suggests a possible functional heterogeneity of inhibitory synapses between different interneurons and CA1 pyramidal cells. 2. We therefore compared inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in CA1 pyramidal cells, which were evoked from two stimulation sites (stratum oriens and stratum radiatum). Stimulation in stratum oriens yielded faster decaying IPSPs and IPSCs than stimulation in stratum radiatum. 3. IPSP and IPSC kinetics were regulated by GABA uptake in both layers as indicated by the prolongation of the signals under tiagabine, a GAT-1 (neuronal GABA plasma membrane transporter)-specific GABA-uptake blocker. However, the effect of tiagabine was significantly more pronounced following stimulation in stratum radiatum than in stratum oriens (prolongation of IPSC half-decay time by 167 vs. 115 %, respectively). 4. In situ hybridization with antisense mRNA for the GABA-synthesizing enzyme glutamate decarboxylase (GAD65/67) and the GABA transporter GAT-1 showed that the proportion of interneurons expressing GAT-1 was lower in stratum oriens than in stratum radiatum/lacunosum-moleculare. 5. From these functional and molecular data we conclude that the regulation of IPSP and IPSC kinetics in CA1 pyramidal cells by neuronal GABA uptake differs between layers. Our findings suggest that this laminar difference is caused by a lower expression of GAT-1 in interneurons in stratum oriens than in stratum radiatum/lacunosum-moleculare.
The Journal of Physiology 12/1998; 512 ( Pt 3):643-9. · 4.72 Impact Factor
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ABSTRACT: The entorhinal cortex (EC) is a major gateway for sensory information into the hippocampal formation. The information flow from layer II and III of the medial EC to the hippocampus is regulated in a frequency dependent manner. Spread of low Mg2+-induced epileptiform activity from EC to hippocampus differs in slices obtained from normal and kindled rats, and in adult versus juvenile rats. In slices from normal rats, low Mg2+-induced epileptiform activity in the EC had only moderate effects on the areas CA3 and CA1, apparently gated by powerful inhibition in the dentate gyrus. In slices from kindled rats, and from juvenile rats, there is facilitated propagation of the seizure-like events and late recurrent discharges through the EC-hippocampal slice. Temporal lobe epilepsy is associated with selective lesions in layer III of the medial EC. Such loss of layer III cells of the medial EC during epilepsy may contribute to the disturbance of frequency dependent information flow from the EC to the hippocampus, and, therefore, to the cognitive impairments associated with these disorders.
Epilepsy Research 10/1998; 32(1-2):183-93. · 2.29 Impact Factor
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ABSTRACT: The superficial cells of the entorhinal cortex (EC), main input to the hippocampus, receive a serotonergic input from the raphe nuclei and express 5-hydroxytryptamine creatine sulfate complex (5-HT) receptors at high density. With the use of intracellular recordings, we investigated the effects of serotonin on synaptic inhibition of layer II and III neurons of the EC. Serotonin reduced both polysynaptic fast and slow inhibitory postsynaptic potentials (IPSPs) in projection neurons of the superficial EC. Polysynaptic fast and slow IPSPs were depressed by serotonin in a dose-dependent manner (0.1-100 microM). Serotonin in a concentration of 1 microM reduced the amplitudes of polysynaptic fast and slow IPSPs by approximately 40 and 50%, respectively. To identify the subtype of the 5-HT-receptor mediating the effects on polysynaptic IPSPs, we applied various 5-HT-receptor agonists and antagonists. Although the serotonin agonists for the 5-HT1B,2C,3 receptors were ineffective, the effects were mimicked by the 5-HT1A-receptor agonists (8-OH-DPAT, 5-CT) and prevented by the 5-HT1A-receptor antagonist NAN-190. To look at the direct effects of 5-HT on inhibitory interneurons, we elicited monosynaptic IPSPs in the absence of excitatory synaptic transmission. In contrast to the polysynaptic IPSPs, monosynaptic IPSPs were not significantly affected by serotonin. Recordings from putative inhibitory interneurons revealed that their excitatory postsynaptic potentials (EPSPs) were reversibly reduced by serotonin. We conclude that serotonin suppresses polysynaptic inhibition in projection neurons of layers II and III of the EC by depression of EPSPs on inhibitory interneurons via 5-HT1A receptors.
Journal of Neurophysiology 10/1998; 80(3):1116-21. · 3.32 Impact Factor
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ABSTRACT: Neuronal oscillations are important for information processing. The entorhinal cortex is one of the structures which is involved in generation of theta rhythm. The major role of the entorhinal cortex is to feed diverse sources of information both to and from the hippocampus. Far from simply being a funnel for this information it becomes clear that the entorhinal cortex has its own active properties that contribute to signal processing. Interestingly, stellate cells in layer II of the entorhinal cortex can intrinsically generate subthreshold, Na+-dependent membrane potential oscillations. Here, using intracellular and patch-clamp recordings, we report a similar phenomenon from neurons of the deep layers of the entorhinal cortex. In our in vitro slice preparation about two-thirds of recorded neurons were able to generate voltage-sensitive subthreshold membrane potential oscillations. At a membrane potential of about 50 mV the mean frequency of the voltage-oscillations was 8.1 Hz, whereby at slightly more positive potentials (-44 mV) the frequency of the membrane potential oscillations was 20 Hz and the oscillations became interrupted by clusters of non-adapting trains of spikes. Pharmacological experiments revealed that the oscillations were not affected by Cs+, but could be blocked by the fast Na+-channel blocker tetrodotoxin. We therefore conclude that voltage- and Na+-dependent subthreshold membrane potential oscillations are not only present in stellate cells of entorhinal cortex-layer II, but are also typical for neurons of the deep layers of the entorhinal cortex.
Neuroscience 09/1998; 85(4):999-1004. · 3.38 Impact Factor
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ABSTRACT: 1. The superficial layers II and III of the entorhinal cortex, which form the main cortical input to the hippocampus, receive a large serotonergic projection from the raphe nuclei and express 5-HT receptors at high density. Here, we studied the effects of serotonin on the intrinsic properties and excitatory synaptic transmission of the superficial medial entorhinal cortex. 2. Intracellular and patch clamp recordings revealed that serotonin hyperpolarized only one-third of the cells, approximately, through a potassium conductance via a GTP-dependent process. 3. Serotonin depressed mixed as well as isolated alpha-amino-3-hydroxy-5-methyl-4-isoxazole- propionic acid receptor (AMPAR)- and N-methyl-D-aspartic acid receptor (NMDAR)-mediated excitatory postsynaptic potentials/currents (EPSPs/EPSCsapproximately 40 % reduction with 1 microM serotonin). 4. The effect of serotonin on EPSPs/EPSCs was similar in whole-cell versus intracellular recordings; it did not require intracellular GTP and was not visible in glutamate applications to excised patches. Miniature EPSCs recorded in the presence of tetrodotoxin and bicuculline were reduced in frequency, but not altered in amplitude. 5. The effects of serotonin on intrinsic properties and EPSPs were partially mimicked by 5-HT1A receptor agonists (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT) and 5-carboxamido-tryptamine maleate (5-CT), and reduced by 5-HT1A receptor antagonists S-(-)-5-fluoro-8-hydroxy-DPAT hydrochloride (S-UH-301), 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide (NAN-190) and spiperone. 6. We conclude that serotonin potently suppresses excitatory synaptic transmission via 5-HT1A receptors in layers II and III of the medial entorhinal cortex by a presynaptic mechanism.
The Journal of Physiology 05/1998; 508 ( Pt 1):119-29. · 4.72 Impact Factor
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ABSTRACT: Intracellular recordings were performed to examine the perforant path projection from layer III of the entorhinal cortex to the subiculum in rat combined hippocampal-entorhinal cortex slices. Electrical stimulation in the medial entorhinal cortex layer III caused short latency combined excitatory and inhibitory synaptic responses in subicular cells. In the presence of the GABA(A) antagonist bicuculline and the GABA(B) antagonist CGP-55845 A inhibition was blocked and isolated AMPA- or NMDA receptor-mediated EPSPs could be elicited. After application of the non-NMDA antagonist NBQX and the NMDA antagonist APV excitatory responses were completely blocked indicating a glutamatergic input from the neurons of the medial entorhinal cortex layer III. By stimulation from a close (< 0.2 mm) position in the presence of NBQX and APV and either CGP-55845 A or bicuculline we could record monosynaptic fast GABA(A) or slow GABA(B) receptor-mediated IPSPs, respectively. We compared synaptic responses in subicular cells induced by stimulation in the medial entorhinal cortex layer III with responses elicited by stimulation of afferent fibres in the alveus. The EPSPs of subicular cells induced by stimulation of alvear fibres could be significantly augmented by simultaneous activation of perforant path fibres originating in the medial entorhinal cortex layer III, while delayed activation of alvear fibres after stimulation of the perforant path resulted in a weak inhibition of the alveus evoked EPSPs. Thus, the perforant path projection activates monosynaptic excitation of subicular neurons. Therefore the entorhinal cortex does not only function as an important input structure of the hippocampal formation but is also able to modulate the hippocampal output via the entorhinal-subicular circuit.
European Journal of Neuroscience 04/1998; 10(3):1011-8. · 3.63 Impact Factor
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ABSTRACT: Storage and retrieval of information in the hippocampus is dependent on information transfer from the entorhinal cortex (EC). We studied how the separate pathways from layer II and III of the EC to the hippocampus are selected for information transfer during repetitive synaptic stimulation. Intracellular recordings were made from EC layer II and III projection cells in horizontal combined EC-hippocampal slices. Synaptic responses to stimulation of deep layers or the lateral EC with stimulus intensities approximately 70% of that required to elicit an action potential were analyzed during short trains of repetitive stimulation. The threshold intensities for induction of action potentials were in layer II cells 8.2 +/- 3.8 (SE) V, significantly larger than 4.4 +/- 1.5 V in type 1, and 5.2 +/- 3.3 V in type 2 layer III cells, respectively. During repetitive subthreshold stimulation with frequencies below 5 Hz the pathway from the EC layer II remained quiet and was preferentially activated with stimulation frequencies above 5 Hz. In contrast the EC layer III cells responded preferentially to low stimulus frequencies (<10 Hz) and became strongly inhibited when synaptically stimulated with frequencies above 10 Hz. Interestingly during stimulus frequencies between 5 and 10 Hz the likelihood that both layer II and III cells fire was large. Thus a frequency switch operates in the entrohinal cortex regulating output of layer II and III cells to the hippocampus. We suggest that such frequency dependent regulation of information flow presents a new principle of neuronal information processing.
Journal of Neurophysiology 12/1997; 78(6):3444-9. · 3.32 Impact Factor
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ABSTRACT: Intracellular recordings were performed to study the effects of 5-HT on membrane properties and EPSP/IPSP responses of subicular neurons in rat combined hippocampal-entorhinal cortex slices. Application of 5-HT induced in 76% of the investigated subicular cells a hyperpolarization and a reduction of membrane resistance. In bursting neurons, 5-HT caused a reduction of the depolarizing envelope underlying burst discharges and attenuated the subsequent afterhyperpolarization. While 5-HT decreased isolated AMPA/kainate and NMDA receptor-mediated responses as well as slow IPSPs, we could not find a consistent effect on isolated fast IPSPs. Since in approximately 25% of subicular neurons EPSPs and slow IPSPs were reduced without any increase of membrane conductance, we conclude that 5-HT has in addition to membrane effects also effects on synaptic currents.
Brain Research 11/1997; 773(1-2):217-22. · 2.73 Impact Factor
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ABSTRACT: The entorhinal cortex projects via layer III neurons directly to the hippocampal area CA1 and the subiculum. We studied the functional properties of the medial entorhinal cortex projection cells in horizontal hippocampal-entorhinal cortex combined slices. These cells displayed, upon single-shock synaptic stimulation, an excitatory postsynaptic potential followed by a fast and/or slow inhibitory postsynaptic potential. Short train repetitive stimulation subthreshold for generation of action potentials induced a slow hyperpolarization of up to 20 s. Pharmacological analysis shows that the slow hyperpolarization could be divided into three components: i) the first component, which lasted 1 s, was sensitive to GABA(B) receptor antagonists; ii) the second component lasting for about 6 s was sensitive to atropine, suggesting muscarinic acetylcholinergic nature of these responses; iii) a late component lasting for up to 20 s was sensitive to naloxone, suggesting a role for opioids in its generation. The finding that layer III projection neurons to the hippocampus proper develop long-lasting hyperpolarizations suggests possible control mechanisms for the output functions of the entorhinal cortex.
Neuroscience 10/1997; 80(1):119-31. · 3.38 Impact Factor
