Relationship of Hippocampal Theta and Gamma Oscillations to Potentiation of Synaptic Transmission

In the hippocampus in vivo, both synaptic plasticity and network activity are closely interdependent. We have found that immediately after an attempt to induce long-term potentiation (LTP), changes in theta (5–10 Hz) and gamma (30–100 Hz) activity correlate tightly with the occurrence of LTP, suggesting that tetanisation-driven activation of sensory inputs synchronises the activity of granule cells and interneurons, and thus, facilitates the encoding of acquired stimuli. This results in increase of theta and gamma power, and elevates the probability that afferent stimuli both coincide with the peak of theta cycle and reach their post-synaptic target within the gamma time-window (of 10–30 ms). Both these mechanisms can effectively shift the direction, of tetanisation-induced changes in synaptic weight, towards potentiation and induction of LTP. Here, we discuss our findings in the context of possible mechanisms that link theta and gamma oscillations with LTP induction, as well as their role in information processing and formation of memories

Hippocampal Network Activity is Transiently Altered by Induction of Long-Term Potentiation in the Dentate Gyrus of Freely Behaving Rats

A role for oscillatory activity in hippocampal neuronal networks has been proposed in sensory encoding, cognitive functions and synaptic plasticity. In the hippocampus, theta (5–10 Hz) and gamma (30–100 Hz) oscillations may provide a mechanism for temporal encoding of information, and the basis for formation and retrieval of memory traces. Long-term potentiation (LTP) of synaptic transmission, a candidate cellular model of synaptic information storage, is typically induced by high-frequency tetanisation (HFT) of afferent pathways. Taking into account the role of oscillatory activity in the processing of information, dynamic changes may occur in hippocampal network activity in the period during HFT and/or soon after it. These changes in rhythmic activity may determine or, at least, contribute to successful potentiation and, in general, to formation of memory. We have found that short-term potentiation (STP) and LTP as well LTP-failure are characterised with different profiles of changes in theta and gamma frequencies. Potentiation of synaptic transmission was associated with a significant increase in the relative theta power and mean amplitude of theta cycles in the period encompassing 300 seconds after HFT. Where LTP or STP, but not failure of potentiation, occurred, this facilitation of theta was accompanied by transient increases in gamma power and in the mean amplitude of gamma oscillations within a single theta cycle. Our data support that specific, correlated changes in these parameters are associated with successful synaptic potentiation. These findings suggest that changes in theta-gamma activity associated with induction of LTP may enable synaptic information storage in the hippocampus

MGluR5 Mediates the Interaction between Late-LTP, Network Activity, and Learning

Hippocampal synaptic plasticity and learning are strongly regulated by metabotropic glutamate receptors (mGluRs) and particularly by mGluR5. Here, we investigated the mechanisms underlying mGluR5-modulation of these phenomena. Prolonged pharmacological blockade of mGluR5 with MPEP produced a profound impairment of spatial memory. Effects were associated with 1) a reduction of mGluR1a-expression in the dentate gyrus; 2) impaired dentate gyrus LTP; 3) enhanced CA1-LTP and 4) suppressed theta (5–10 Hz) and gamma (30–100 Hz) oscillations in the dentate gyrus. Allosteric potentiation of mGluR1 after mGluR5 blockade significantly ameliorated dentate gyrus LTP, as well as suppression of gamma oscillatory activity. CA3-lesioning prevented MPEP effects on CA1-LTP, suggesting that plasticity levels in CA1 are driven by mGluR5-dependent synaptic and network activity in the dentate gyrus. These data support the hypothesis that prolonged mGluR5-inactivation causes altered hippocampal LTP levels and network activity, which is mediated in part by impaired mGluR1-expression in the dentate gyrus. The consequence is impairment of long-term learning

The Low-Threshold Calcium Channel Cav3.2 Mediates Burst Firing of Mature Dentate Granule Cells

International audienceMature granule cells are poorly excitable neurons that were recently shown to fire action potentials, preferentially in bursts. It is believed that the particularly pronounced short-term facilitation of mossy fiber synapses makes granule cell bursting a very effective means of properly transferring information to CA3. However, the mechanism underlying the unique bursting behavior of mature granule cells is currently unknown. Here, we show that Cav3.2 T-type channels at the axon initial segment are responsible for burst firing of mature granule cells in rats and mice. Accordingly, Cav3.2 knockout mice fire tonic spikes and exhibit impaired bursting, synaptic plasticity and dentate-to-CA3 communication. The data show that Cav3.2 channels are strong modulators of bursting and can be considered a critical molecular switch that enables effective information transfer from mature granule cells to the CA3 pyramids

Brain extracellular matrix retains connectivity in neuronal networks

The formation and maintenance of connectivity are critically important for the processing and storage of information in neuronal networks. The brain extracellular matrix (ECM) appears during postnatal development and surrounds most neurons in the adult mammalian brain. Importantly, the removal of the ECM was shown to improve plasticity and post-traumatic recovery in the CNS, but little is known about the mechanisms. Here, we investigated the role of the ECM in the regulation of the network activity in dissociated hippocampal cultures grown on microelectrode arrays (MEAs). We found that enzymatic removal of the ECM in mature cultures led to transient enhancement of neuronal activity, but prevented disinhibition-induced hyperexcitability that was evident in age-matched control cultures with intact ECM. Furthermore, the ECM degradation followed by disinhibition strongly affected the network interaction so that it strongly resembled the juvenile pattern seen in naïve developing cultures. Taken together, our results demonstrate that the ECM plays an important role in retention of existing connectivity in mature neuronal networks that can be exerted through synaptic confinement of glutamate. On the other hand, removal of the ECM can play a permissive role in modification of connectivity and adaptive exploration of novel network architecture

Dynamic compartmentalization of calcium channel signalling in neurons

Calcium fluxes through the neuronal membrane are strictly limited in time due to biophysical properties of voltage-gated and ligand-activated ion channels and receptors. Being embedded into the crowded dynamic environment of biological membranes, Ca2+-permeable receptors and channels undergo perpetual spatial rearrangement, which enables their temporary association and formation of transient signalling complexes. Thus, efficient calcium-mediated signal transduction requires mechanisms to support very precise spatiotemporal alignment of the calcium source and Ca2+-binding lipids and proteins in a highly dynamic environment. The mobility of calcium channels and calcium-sensing proteins themselves can be considered as a physiologically meaningful variable that affects calcium-mediated signalling in neurons. In this review, we will focus on voltage-gated calcium channels (VGCCs) and activity-induced relocation of stromal interaction molecules (STIMs) in the endoplasmic reticulum (ER) to show that particularly in time ranges between milliseconds to minutes, dynamic rearrangement of calcium conducting channels and sensor molecules is of physiological relevance. This article is part of the special issue entitled 'Mobility and trafficking of neuronal membrane proteins'