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Ole Paulsen

Publications and source records attributed to Ole Paulsen.

15 recordsLinked to original sources

Synaptic currents in anatomically identified CA3 neurons during hippocampal gamma oscillations in vitro.

Gamma-frequency oscillations are prominent during active network states in the hippocampus. An intrahippocampal gamma generator has been identified in the CA3 region. To better understand the synaptic mechanisms involved in gamma oscillogenesis, we recorded action potentials and synaptic currents in distinct types of anatomically identified CA3 neurons during carbachol-induced (20-25 microM) gamma oscillations in rat hippocampal slices. We wanted to compare and contrast the relationship between excitatory and inhibitory postsynaptic currents in pyramidal cells and perisomatic-targeting interneurons, cell types implicated in gamma oscillogenesis, as well as in other interneuron subtypes, and to relate synaptic currents to the firing properties of the cells. We found that phasic synaptic input differed between cell classes. Most strikingly, the dominant phasic input to pyramidal neurons was inhibitory, whereas phase-coupled perisomatic-targeting interneurons often received a strong phasic excitatory input. Differences in synaptic input could account for some of the differences in firing rate, action potential phase precision, and mean action potential phase angle, both between individual cells and between cell types. There was a strong positive correlation between the ratio of phasic synaptic excitation to inhibition and firing rate over all neurons and between the phase precision of excitation and action potentials in interneurons. Moreover, mean action potential phase angle correlated with the phase of the peak of the net-estimated synaptic reversal potential in all phase-coupled neurons. The data support a recurrent mechanism of gamma oscillations, whereby spike timing is controlled primarily by inhibition in pyramidal cells and by excitation in interneurons.

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Keeping inhibition timely.

GABAergic interneurons play a key role in orchestrating cortical network oscillations. In this issue of Neuron, two studies (Bacci and Huguenard and Vida et al.) identify how networks of fast-spiking interneurons can enhance the regularity, precision, and robustness of their own rhythmicity via individual and collective self-innervation.

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Matching storage and recall: hippocampal spike timing-dependent plasticity and phase response curves.

Hippocampal area CA3 is widely considered to function as an autoassociative memory. However, it is insufficiently understood how it does so. In particular, the extensive experimental evidence for the importance of carefully regulated spiking times poses the question as to how spike timing-based dynamics may support memory functions. Here, we develop a normative theory of autoassociative memory encompassing such network dynamics. Our theory specifies the way that the synaptic plasticity rule of a memory constrains the form of neuronal interactions that will retrieve memories optimally. If memories are stored by spike timing-dependent plasticity, neuronal interactions should be formalized in terms of a phase response curve, indicating the effect of presynaptic spikes on the timing of postsynaptic spikes. We show through simulation that such memories are competent analog autoassociators and demonstrate directly that the attributes of phase response curves of CA3 pyramidal cells recorded in vitro qualitatively conform with the theory.

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Perisomatic feedback inhibition underlies cholinergically induced fast network oscillations in the rat hippocampus in vitro.

Gamma frequency network oscillations are assumed to be important in cognitive processes, including hippocampal memory operations, but the precise functions of these oscillations remain unknown. Here, we examine the cellular and network mechanisms underlying carbachol-induced fast network oscillations in the hippocampus in vitro, which closely resemble hippocampal gamma oscillations in the behaving rat. Using a combination of planar multielectrode array recordings, imaging with voltage-sensitive dyes, and recordings from single hippocampal neurons within the CA3 gamma generator, active current sinks and sources were localized to the stratum pyramidale. These proximal currents were driven by phase-locked rhythmic inhibitory inputs to pyramidal cells from identified perisomatic-targeting interneurons. AMPA receptor-mediated recurrent excitation was necessary for the synchronization of interneuronal discharge, which strongly supports a synaptic feedback model for the generation of hippocampal gamma oscillations.

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Mechanisms underlying gamma ('40 Hz') network oscillations in the hippocampus--a mini-review.

Gamma-frequency oscillations (approximately 30-100 Hz) in cortical network activity have been proposed to provide a temporal structure for various forms of cognitive processing. This review provides an update on recent experiments addressing the mechanisms underlying gamma-frequency network oscillations in the rodent hippocampus. Particular emphasis is placed on the correlation between in vivo observations and in vitro models.

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Hippocampal gamma-frequency oscillations: from interneurones to pyramidal cells, and back.

GABAergic interneurones are necessary for the emergence of hippocampal gamma-frequency network oscillations, during which they play a key role in the synchronization of pyramidal cell firing. However, it remains to be resolved how distinct interneurone subtypes contribute to gamma-frequency oscillations, in what way the spatiotemporal pattern of interneuronal input affects principal cell activity, and by which mechanisms the interneurones themselves are synchronized. Here we summarize recent evidence from cholinergically induced gamma-frequency network oscillations in vitro, showing that perisomatic-targeting GABAergic interneurones provide prominent rhythmic inhibition in pyramidal cells, and that these interneurones are synchronized by recurrent excitation. We conclude by presenting a minimal integrate-and-fire network model which demonstrates that this excitatory-inhibitory feedback loop is sufficient to explain the generation of intrahippocampal gamma-frequency oscillations.

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Dissociation of experience-dependent and -independent changes in excitatory synaptic transmission during development of barrel cortex.

A fundamental problem in the study of cortical development is the extent to which the formation and refinement of synaptic circuitry depends upon sensory experience. The barrel cortex is a useful model system to study experience-dependent cortical development because there is a simple mapping of individual whiskers to the corresponding barrel columns in the cortex. We investigated experience-dependent and -independent changes in glutamatergic synaptic transmission in the barrel cortex during the second postnatal week by comparing synaptic responses from whisker-intact mice at postnatal day (P) 7 and P14 with those from whisker-deprived mice at P14. alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA)-receptor-mediated excitatory synaptic responses were recorded from layer 2/3 pyramidal cells in vitro during voltage-clamp in response to stimulation in layer 4. We observed that the ratio of synaptic AMPA- to NMDA-receptor-mediated current (A/N ratio) increased with developmental age. The development of the A/N ratio was unchanged by deprivation of the whisker input throughout the second postnatal week. In contrast, the NMDA-receptor current decay and sensitivity to the NMDA receptor 2B subunit-selective antagonist ifenprodil was affected strongly by such deprivation. These results demonstrate a concurrent dissociation between sensory experience-dependent and -independent changes of glutamatergic transmission in the barrel cortex during the second postnatal week. Furthermore, they suggest that the development of subunit composition of synaptic receptors is dependent on sensory experience, whereas maturation of the synaptic A/N ratio is independent of such experience. Thus, different components of synaptic development may be governed by different developmental rules.

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Spike timing of distinct types of GABAergic interneuron during hippocampal gamma oscillations in vitro.

Gamma frequency (30-100 Hz) network oscillations occur in the intact hippocampus during awake, attentive behavior. Here, we explored the underlying cellular mechanisms in an in vitro model of persistent gamma-frequency oscillations, induced by bath application of 20 microm carbachol in submerged hippocampal slices at 30 +/- 1 degrees C. Current-source density analysis of the field oscillation revealed a prominent alternating sink-source pair in the perisomatic and apical dendritic regions of CA3. To elucidate the active events generating these extracellular dipoles, we examined the firing properties of distinct neuron types. Visually guided unit recordings were obtained from individual CA3 neurons followed by intracellular labeling for anatomical identification. Pyramidal cells fired at 2.82 +/- 0.7 Hz, close to the negative peak of the oscillation (0.03 +/- 0.65 msec), and often in conjunction with a negative spike-like component of the field potential. In contrast, all phase-coupled interneurons fired after this negative peak. Perisomatic inhibitory interneurons fired at high frequency (18.1 +/- 2.7 Hz), shortly after the negative peak (1.97 +/- 0.95 msec) and were strongly phase-coupled. Dendritic inhibitory interneurons fired at lower frequency (8.4 +/- 2.4 Hz) and with less fidelity and a longer delay after the negative peak (4.3 +/- 1.1 msec), whereas interneurons with cell body in the stratum radiatum often showed no phase relationship with the field oscillation. The phase and spike time data of individual neurons, together with the current-source density analysis, support a synaptic feedback model of gamma oscillations primarily involving pyramidal cells and inhibitory cells targeting their perisomatic region.

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Preferential origin and layer destination of GAD65-GFP cortical interneurons.

To identify the origin and track the migratory pathway of specific subpopulations of GABAergic interneurons, we studied tangential migration in a recently developed GAD65-GFP transgenic mouse strain. First, we used immunohistochemical methods to characterize the expression of specific neurochemical markers in the GAD65-GFP neurons. Then, organotypic cultures were used in combination with birth-dating studies to determine the time of generation, place of origin and migratory route of these cells. From E14 to E15, the highest density of GAD65-GFP cells was seen in the lower intermediate zone; however, at later stages more GAD65-GFP cells were observed in the subventricular zone. Migratory GAD65-GFP cells express GAD65, but not calretinin or reelin. Surprisingly, only 4% were calbindin immunopositive. At P21, GAD65-GFP cells were found predominantly in layers II-III and expressed calretinin and neuropeptide Y. Remarkably, almost all cholecystokinin-positive but very few parvalbumin-positive neurons expressed GFP. In vitro studies demonstrated that the caudal ganglionic eminence gives rise to a large proportion of GAD65-GFP interneurons and in vivo birth-dating experiments showed that GAD65-GFP interneurons in supragranular layers are born at late embryonic development. Taken together these results support the idea that the destination layer of GABAergic interneurons is closely linked to their place of origin and time of generation.

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Properties of horizontal axo-axonic cells in stratum oriens of the hippocampal CA1 area of rats in vitro.

Local-circuit gamma-aminobutyric acid (GABA)ergic interneurons constitute a diverse population of cells, which remain poorly defined into functionally distinct subclasses. Traditionally, dendritic and axonal arbors have been used to describe cell classes. In the present report, we characterize a set of hippocampal interneurons, horizontal axo-axonic cells, located in stratum oriens. They displayed the pattern of axonal arborization characteristic of axo-axonic cells with radially aligned rows of boutons making synapses exclusively on axon initial segments of pyramidal cells, as shown by electron microscopy. However, in contrast to previously described axo-axonic cells, which have radial dendrites spanning all layers, the dendrites of the horizontal axo-axonic cells were restricted to stratum oriens and ran parallel with the layers for several hundred micrometers. Single action potentials elicited by depolarizing current steps in these cells were often followed by a fast- and medium-duration afterhyperpolarization, distinguishing them from fast-spiking interneurons. In two out of four cells, trains of action potentials showed prominent early spike frequency adaptation and a characteristic "accommodative hump." Excitatory postsynaptic potentials (EPSPs) could be evoked by stimuli delivered to stratum oriens. Paired recordings unequivocally confirmed direct synaptic inputs from CA1 pyramidal cells. The kinetics of the EPSPs were fast (rise time 1.7 +/- 0.6 ms, mean +/- SD, n = 3; decay time constant 19.3 +/- 2.4 ms). They showed paired-pulse depression with inter-stimulus intervals of 10-50 ms. One pair showed a reciprocal connection establishing a direct feedback loop. The axo-axonic cell-evoked inhibitory postsynaptic potentials (IPSPs) were reliable (failure rate approximately 10%). Our data show that the laminar distribution of the dendrites of axo-axonic cells can vary, suggesting distinct synaptic inputs. However, this remains to be shown directly, and we cannot exclude the possibility that all axo-axonic cells may gather similar synaptic input, leaving them as one distinct class of interneuron.

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Maturation of long-term potentiation induction rules in rodent hippocampus: role of GABAergic inhibition.

The induction rules of synaptic plasticity are important for the functional operation of a neural network. We asked whether such synaptic plasticity rules change during development from juvenile to adult animals. Using perforated patch and whole-cell recordings from CA1 pyramidal cells in hippocampal slices, we demonstrate here that the postsynaptic requirements for induction of associative long-term potentiation (LTP) shift gradually. Presynaptic stimulation paired with single postsynaptic action potentials became progressively less effective at inducing LTP with advancing developmental age until, in adult hippocampus, postsynaptic bursts of action potentials were necessary to induce synaptic potentiation. This developmental change might be accounted for by changes in GABA(A) receptor-mediated inhibition known to occur in the hippocampus during this postnatal period, because blocking GABA(A) receptor-mediated inhibition re-established the effectiveness of single postsynaptic action potentials at inducing LTP in adult hippocampus. These data reveal a gradual shift in the induction rules for LTP, explained by a maturational change in GABAergic inhibition, and could have implications for our understanding of the role of inhibition in information processing in the brain.

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Blockade of GABA(B) receptors alters the tangential migration of cortical neurons.

To better understand the role of neurotransmitter receptors in neuronal differentiation and maturation a detailed knowledge of their identity, location and function in the plasma membrane of specific neuronal populations during development is required. Combining pre-embedding immunocytochemistry with cell tracking in embryonic brain slice cultures we show that virtually all neurons (approximately 98%) migrating through the lower intermediate zone (LIZ) on their way from the medial ganglionic eminence to the cerebral cortex, express GABA(B)R1. Blockade of GABA(B)Rs with a specific antagonist, CGP52432, resulted in a concentration-dependent accumulation of these tangentially migrating neurons in the ventricular/sub-ventricular zones (VZ/SVZ) of the cortex and fewer cells were observed in the cortical plate/marginal zone (CP/MZ) and LIZ. Moreover, they had significantly shorter leading processes compared with similar migrating cells in control slices. Electrophysiological recording in LIZ and CP cells revealed no direct effect of either CGP52432 or the GABA(B)R agonist, baclofen, on resting membrane properties suggesting that the effect of CGP52432 on migration might be mediated through a metabotropic action or the regulation of release of factors controlling migration. These results suggest that GABA(B)Rs have an important modulatory role in the migration of cortical interneurons.

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