@article{3445, abstract = {The medial septal region and the hippocampus are connected reciprocally via GABAergic neurons, but the physiological role of this loop is still not well understood. In an attempt to reveal the physiological effects of the hippocamposeptal GABAergic projection, we cross-correlated hippocampal sharp wave (SPW) ripples or theta activity and extracellular units recorded in the medial septum and diagonal band of Broca (MSDB) in freely moving rats. The majority of single MSDB cells (60%) were significantly suppressed during SPWs. Most cells inhibited during SPW (80%) fired rhythmically and phase-locked to the negative peak of the CA1 pyramidal layer theta waves. Because both SPW and the negative peak of local theta waves correspond to the maximum discharge probability of CA1 pyramidal cells and interneuron classes, the findings indicate that the activity of medial septal neurons can be negatively (during SPW) or positively (during theta waves) correlated with the activity of hippocampal interneurons. We hypothesize that the functional coupling between medial septal neurons and hippocampal interneurons varies in a state-dependent manner.}, author = {Dragoi, George and Carpi, Daniel and Recce, Michael and Csicsvari, Jozsef L and Buzsáki, György}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {14}, pages = {6191 -- 6199}, publisher = {Society for Neuroscience}, title = {{Interactions between hippocampus and medial septum during sharp waves and theta oscillation in the behaving rat}}, doi = {10.1523/JNEUROSCI.19-14-06191.1999}, volume = {19}, year = {1999}, } @article{3518, abstract = {Information in neuronal networks may be represented by the spatiotemporal patterns of spikes. Here we examined the temporal coordination of pyramidal cell spikes in the rat hippocampus during slow-wave sleep. In addition, rats were trained to run in a defined position in space (running wheel) to activate a selected group of pyramidal cells. A template-matching method and a joint probability map method were used for sequence search. Repeating spike sequences in excess of chance occurrence were examined by comparing the number of repeating sequences in the original spike trains and in surrogate trains after Monte Carlo shuffling of the spikes. Four different shuffling procedures were used to control for the population dynamics of hippocampal neurons. Repeating spike sequences in the recorded cell assemblies were present in both the awake and sleeping animal in excess of what might be predicted by random variations. Spike sequences observed during wheel running were “replayed” at a faster timescale during single sharp-wave bursts of slow-wave sleep. We hypothesize that the endogenously expressed spike sequences during sleep reflect reactivation of the circuitry modified by previous experience. Reactivation of acquired sequences may serve to consolidate information.}, author = {Nádasdy, Zoltán and Hirase, Hajima and Czurkó, András and Csicsvari, Jozsef L and Buzsáki, György}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {21}, pages = {9497 -- 9507}, publisher = {Society for Neuroscience}, title = {{Replay and time compression of recurring spike sequences in the hippocampus}}, doi = {10.1523/JNEUROSCI.19-21-09497.1999}, volume = {19}, year = {1999}, } @article{3524, abstract = {We examined whether excitation and inhibition are balanced in hippocampal cortical networks. Extracellular field and single-unit activity were recorded by multiple tetrodes and multisite silicon probes to reveal the timing of the activity of hippocampal CAI pyramidal cells and classes of interneurons during theta waves and sharp wave burst (SPW)-associated field ripples. The somatic and dendritic inhibition of pyramidal cells was deduced from the activity of interneurons in the pyramidal layer [int(p)] and in the alveus and st. oriens [int(a/o)], respectively. int(p) and int(a/o) discharged an average of 60 and 20 degrees before the population discharge of pyramidal cells during the theta cycle, respectively. SPW ripples were associated with a 2.5-fold net increase of excitation. The discharge frequency of int(a/o) increased, decreased (”anti-SPW” cells), or did not change (”SPW-independent” cells) during SPW suggesting that not all interneurons are innervated by pyramidal cells. Int(p) either fired together with (unimodal cells) or both before and after (bimodal cells) the pyramidal cell burst. During fast-ripple oscillation, the activity of interneurons in both the int(p) and int(a/o) groups lagged the maximum discharge probability of pyramidal neurons by 1-2 msec. Network state changes, as reflected by field activity, covaried with changes in the spike train dynamics of single cells and their interactions. Summed activity of parallel-recorded interneurons, but not of pyramidal cells, reliably predicted theta cycles, whereas the reverse was true for the ripple cycles of SPWs. We suggest that network-driven excitability changes provide temporal windows of opportunity for single pyramidal cells to suppress, enable, or facilitate selective synaptic inputs.}, author = {Csicsvari, Jozsef L and Hirase, Hajima and Czurkó, András and Mamiya, Akira and Buzsáki, György}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {1}, pages = {274 -- 287}, publisher = {Society for Neuroscience}, title = {{Oscillatory coupling of hippocampal pyramidal cells and interneurons in the behaving rat}}, doi = {10.1523/JNEUROSCI.19-01-00274.1999}, volume = {19}, year = {1999}, } @article{3488, abstract = {We have examined gating and pharmacological characteristics of somatic K+ channels in fast-spiking interneurons and regularly spiking principal neurons of hippocampal slices. In nucleated patches isolated from basket cells of the dentate gyrus, a fast delayed rectifier K+ current component that was highly sensitive to tetraethylammonium (TEA) and 4-aminopyridine (4- AP) (half-maximal inhibitory concentrations <0.1 mM) predominated, contributing an average of 58% to the total K+ current in these cells. By contrast, in pyramidal neurons of the CA1 region a rapidly inactivating A- type K+ current component that was TEA-resistant prevailed, contributing 61% to the total K+ current. Both types of neurons also showed small amounts of the K+ current component mainly found in the other type of neuron and, in addition, a slow delayed rectifier K+ current component with intermediate properties (sow inactivation, intermediate sensitivity to TEA). Single-cell RT-PCR analysis of mRNA revealed that Kv3 (Kv3.1, Kv3.2) subunit transcripts were expressed in almost all (89%) of the interneurons but only in 17% of the pyramidal neurons. In contrast, Kv4 (Kv4.2, Kv4.3) subunit mRNAs were present in 87% of pyramidal neurons but only in 55% of interneurons. Selective block of fast delayed rectifier K+ channels, presumably assembled from Kv3 subunits, by 4-AP reduced substantially the action potential frequency in interneurons. These results indicate that the differential expression of Kv3 and Kv4 subunits shapes the action potential phenotypes of principal neurons and interneurons in the cortex.}, author = {Martina, Marco and Schultz, Jobst and Ehmke, Heimo and Monyer, Hannah and Jonas, Peter M}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {20}, pages = {8111 -- 8125}, publisher = {Society for Neuroscience}, title = {{Functional and molecular differences between voltage-gated K+ channels of fast-spiking interneurons and pyramidal neurons of rat hippocampus}}, doi = {10.1523/JNEUROSCI.18-20-08111.1998}, volume = {18}, year = {1998}, } @article{2582, abstract = {Neurotransmission in the hippocampus is modulated variously through presynaptic metabotropic glutamate receptors (mGluRs). To establish the precise localization of presynaptic mGluRs in the rat hippocampus, we used subtype-specific antibodies for eight mGluRs (mGluR1-mGluR8) for immunohistochemistry combined with lesioning of the three major hippocampal pathways: the perforant path, mossy fiber, and Schaffer collateral. Immunoreactivity for group II (mGluR2) and group III (mGluR4a, mGluR7a, mGluR7b, and mGluR8) mGluRs was predominantly localized to presynaptic elements, whereas that for group I mGluRs (mGluR1 and mGluR5) was localized to postsynaptic elements. The medial perforant path was strongly immunoreactive for mGluR2 and mGluR7a throughout the hippocampus, and the lateral perforant path was prominently immunoreactive for mGluR8 in the dentate gyrus and CA3 area. The messy fiber was labeled for mGluR2, mGluR7a, and mGluR7b, whereas the Schaffer collateral was labeled only for mGluR7a. Electron microscopy further revealed the spatial segregation of group II and group III mGluRs within presynaptic elements. Immunolabeling for the group III receptors was predominantly observed in presynaptic active zones of asymmetrical and symmetrical synapses, whereas that for the group II receptor (mGluR2) was found in preterminal rather than terminal portions of axons. Target cell-specific segregation of receptors, first reported for mGluR7a (Shigemoto et al., 1996), was also apparent for the other group III mGluRs, suggesting that transmitter release is differentially regulated by 2-amino- 4-phosphonobutyrate-sensitive mGluRs in individual synapses on single axons according to the identity of postsynaptic neurons.}, author = {Shigemoto, Ryuichi and Kinoshita, Ayae and Wada, Eiki and Nomura, Sakashi and Ohishi, Hitoshi and Takada, Masahiko and Flor, Peter and Neki, Akio and Abe, Takaaki and Nakanishi, Shigetada and Mizuno, Noboru}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {19}, pages = {7503 -- 7522}, publisher = {Society for Neuroscience}, title = {{Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus}}, doi = {10.1523/JNEUROSCI.17-19-07503.1997}, volume = {17}, year = {1997}, } @article{3482, abstract = {AMPA- and NMDA-type glutamate receptors (AMPARs and NMDARs) mediate excitatory synoptic transmission in the basal ganglia and may contribute to excitotoxic injury. We investigated the functional properties of AMPARs and NMDARs expressed by six main types of basal ganglia neurons in acute rat brain slices (principal neurons and cholinergic interneurons of striatum, GABAergic and dopaminergic neurons of substantia nigra, globus pallidus neurons, and subthalamic nucleus neurons) using fast application of glutamate to nucleated and outside-out membrane patches, AMPARs in different types of basal ganglia neurons were functionally distinct. Those expressed in striatal principal neurons exhibited the slowest gating (desensitization time constant τ = 11.5 msec, 1 mM glutamate, 22°C), whereas those in striatal cholinergic interneurons showed the fastest gating (desensitization time constant τ = 3.6 msec). The lowest Ca2+ permeability of AMPARs was observed in nigral dopaminergic neurons (P(CA)/P(NA) = 0.10), whereas the highest Ca2+ permeability was found in subthalamic nucleus neurons (P(Ca)/P(Na) = 1.17). NMDARs of different types of basal ganglia neurons were less variable in their functional properties; those expressed in nigral dopaminergic neurons exhibited the slowest gating (deactivation time constant of predominant fast component τ1 150 msec, 100 μM glutamate), and those of globus pallidus neurons showed the fastest gating (τ1 = 67 msec). The Mg2+ block of NMDARs was similar; the average chord conductance ratio g(+60mv)/g(+40mV) was 0.18-0.22 in 100 μM external Mg2+. Hence, AMPARs expressed in different types of basal ganglia neurons are markedly diverse, whereas NMDARs are less variable in functional properties that are relevant for excitatory synoptic transmission and neuronal vulnerability.}, author = {Götz, Thomas and Kraushaar, Udo and Geiger, Jörg and Lubke, Joachim and Berger, Thomas and Jonas, Peter M}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {1}, pages = {204 -- 215}, publisher = {Society for Neuroscience}, title = {{Functional properties of AMPA and NMDA receptors expressed in identified types of basal ganglia neurons}}, doi = {10.1523/JNEUROSCI.17-01-00204.1997}, volume = {17}, year = {1997}, } @article{3483, abstract = {The main excitatory pathway of the hippocampal formation is controlled by a network of morphologically distinct populations of GABAergic interneurons. Here we describe a novel type of GABAergic interneuron located in the outer molecular layer (OML) of the rat dentate gyrus with a long- range forward projection from the dentate gyrus to the subiculum across the hippocampal fissure, OML interneurons were recorded in hippocampal slices by using the whole-cell patch-clamp configuration. During recording, cells were filled with biocytin for subsequent light and electron microscopic analysis. Neurons projecting to the subiculum were distributed throughout the entire OML. They had round or ovoid somata and a multipolar dendritic morphology. Two axonal domains could be distinguished: an extensive, tangential distribution within the OML and a long-range vertical and tangential projection to layer 1 and stratum pyramidale of the subiculum. Symmetric synaptic contacts were established by these interneurons on dendritic shafts in the OML and subiculum. OML interneurons were characterized physiologically by short action potential duration and marked afterhyperpolarization that followed the spike. On sustained current injection, they generated high- frequency (up to 130 Hz, 34°C) trains of action potentials with only little adaptation. In situ hybridization and single-call RT-PCR analysis for GAD67 mRNA confirmed the GABAergic nature of OML interneurons. GABAergic interneurons in the OML projecting to the subiculum connect the input and output regions of the hippocampus. Hence, they could mediate long-range feed- forward inhibition and may participate in an oscillating cross-regional interneuron network that may synchronize the activity of spatially distributed principal neurons in the dentate gyrus and the subiculum.}, author = {Ceranik, Katya and Bender, Roland and Geiger, Jörg and Monyer, Hannah and Jonas, Peter M and Frotscher, Michael and Lubke, Joachim}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {14}, pages = {5380 -- 5394}, publisher = {Society for Neuroscience}, title = {{A novel type of GABAergic interneuron connecting the input and the output regions of the hippocampus.}}, doi = {10.1523/JNEUROSCI.17-14-05380.1997}, volume = {17}, year = {1997}, } @article{3476, abstract = {Tight-seal whole-cell recordings were made from cleaned somata of CA3 pyramidal cells deep in hippocampal slices from 19–21-d-old rats. The cells were filled with biocytin, and their voltage responses to short current pulses were recorded. After washout of initial sag, responses scaled linearly with injected current and were stable over time. The dendritic and axonal arbors of four cells were reconstructed and measured using light microscopy. Dendritic spines and axonal boutons were counted and the additional membrane area was incorporated into the relevant segments. The morphology of each neuron was converted into a detailed branching cable model by assuming values for specific membrane capacitance Cm and resistance Rm, and cytoplasmic resistivity Ri. These parameters were optimized for each cell by directly matching the model's response to that of the real cell by means of a modified weighted least-squares fitting procedure. By comparing the deviations between model and experimental responses to control noise recordings, approximate 95% confidence intervals were established for each parameter. If a somatic shunt was allowed, a wide range of possible Rm values produced acceptable fits. With zero shunt, Cm was 0.7–0.8 microFcm-2, Ri was 170–340 omega cm, and Rm ranged between 120 and 200 k omega cm2. The electrotonic lengths of the basal and oblique dendrites were 0.2–0.3 space constants, and those of the apical tufts were 0.4–0.7 space constants. The steady-state electrical geometry of these cells was therefore compact; average dendritic tip/soma relative synaptic efficacies were > 93% for the basal and oblique dendrites, and > 81% for the tufts. With fast transient synaptic inputs, however, the models produced a wide range of postsynaptic potential shapes and marked filtering of voltage-clamp currents.}, author = {Major, Guy and Larkman, Alan and Jonas, Peter M and Sakmann, Bert and Jack, Julian}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {8}, pages = {4613 -- 4638}, publisher = {Society for Neuroscience}, title = {{Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices}}, doi = {10.1523/JNEUROSCI.14-08-04613.1994}, volume = {14}, year = {1994}, } @article{2537, abstract = {The metabotropic glutamate receptors are coupled to intracellular signal transduction via G-proteins and consist of a family of at least five different subtypes, termed mGluR1-mGluR5. We studied the signal transduction mechanism and pharmacological characteristics of the rat mGluR3 and mGluR4 subtypes in Chinese hamster ovary cells permanently expressing the cloned receptors. Both mGluR3 and mGluR4 inhibit the forskolin-stimulated accumulation of intracellular cAMP formation in response to agonist interaction. Consistent with the high degree of sequence similarity to mGluR2, mGluR3 closely resembles mGluR2 in its agonist selectivity; the potency rank order of agonists is L-glutamate > trans-1-aminocyclopentane- 1,3-dicarboxylate > ibotenate > quisqualate. mGluR4 is totally different in its agonist specificity from any other member of the metabotropic receptors. This receptor potently reacts with L-2-amino-4-phosphonobutyrate(L-AP4) in a stereo-selective manner and moderately responds to L-serine-O-phosphate. mGluR4 thus corresponds well to the putative L-AP4 receptor characterized from brain preparations. Blot and in situ hybridization analyses indicated that both mRNAs are widely distributed in the rat brain. mGluR3 mRNA is highly expressed in neuronal cells of the cerebral cortex and the caudate- putamen, and in granule cells of the hippocampal dentate gyrus. The expression pattern of mGluR4 mRNA is more restricted, and this expression is prominent in the cerebellum, olfactory bulb, and thalamus. Furthermore, the mGluR3 mRNA, unlike the other mRNAs for the metabotropic receptors, is highly expressed in glial cells throughout the brain regions. The metabotropic glutamate receptor subtypes can thus be classified into three subgroups according to the similarity in their amino acid sequences, signal transduction, and agonist selectivity: mGluR1/mGluR5, mGluR2/mGluR3, and mGluR4. The mRNAs for the individual receptor subtypes, however, show overlapping but distinct patterns of expression in the rat CNS.}, author = {Tanabe, Yasuto and Nomura, Akinori and Masu, Masayuki and Shigemoto, Ryuichi and Mizuno, Noboru and Nakanishi, Shigetada}, issn = {0270-6474}, journal = {Journal of Neuroscience}, number = {4}, pages = {1372 -- 1378}, publisher = {Society for Neuroscience}, title = {{Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4}}, doi = {10.1523/JNEUROSCI.13-04-01372.1993}, volume = {13}, year = {1993}, }