Adrenergic modulation of sharp wave‐ripple activity in rat hippocampal slices
ABSTRACT Norepinephrine (NE) has been shown to facilitate learning and memory by modulating synaptic plasticity in the hippocampus in vivo. During memory consolidation, transiently stored information is transferred from the hippocampus into the cortical mantle. This process is believed to depend on the generation of sharp wave-ripple complexes (SPW-Rs), during which previously stored information might be replayed. Here, we used rat hippocampal slices to investigate neuromodulatory effects of NE on SPW-Rs, induced by a standard long-term potentiation (LTP) protocol, in the CA3 and CA1. NE (10–50 μM) dose-dependently and reversibly suppressed the generation of SPW-Rs via activation of α1 adrenoreceptors, as indicated by the similar effects of phenylephrine (100 μM). In contrast, the unspecific β adrenoreceptor agonist isoproterenol (2 μM) significantly increased the incidence of SPW-Rs. Furthermore, β adrenoreceptor activation significantly facilitated induction of both LTP and SPW-Rs within the CA3 network. Suppression of SPW-Rs by NE was associated with a moderate hyperpolarization in the majority of CA3 pyramidal cells and with a reduction of presynaptic Ca2+ uptake in the stratum radiatum. This was indicated by activity-dependent changes in [Ca2+]o and Ca2+fluorescence signals, by changes in the paired pulse ratio of evoked EPSPs and by analysis of the coefficient of variance. In the presence of NE, repeated high frequency stimulation (high-frequency stimulation (HFS)) failed to induce SPW-Rs, although SPW-Rs appeared following washout of NE. Together, our data indicate that the NE-mediated suppression of hippocampal SPW-Rs depends on α1 adrenoreceptor activation, while their expression and activity-dependent induction is facilitated via β1-adrenoreceptors. © 2011 Wiley Periodicals, Inc.
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ABSTRACT: Sharp wave-ripple complexes (SPW-R) are observed in vivo during resting immobility, consummatory behavior and during slow wave sleep, and they have been proposed to support memory consolidation. It has been suggested that GABAergic cells play important roles in controlling incidence of sharp waves and of ripple frequency. We report here that the GABAB agonist baclofen reversibly suppresses SPW-R activity in rat hippocampal slices, presumably affecting the strength of neuronal coupling in the associative network of area CA3. The effect is specific as the GABAB receptor antagonist CGP55846 prevents this effect; however, CGP55846 application had no major effect on incidence of SPW-R. Interestingly, repetitive stimulation in the presence of baclofen is able to induce SPW-R activity, which only appears after washout of baclofen. Our findings suggest that GABA levels through activation of GABAB receptors may be involved in the transition from theta-gamma to SPW-R working mode in the hippocampus.Neuroscience Letters 05/2014; · 2.06 Impact Factor
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ABSTRACT: Norepinephrine acting via β-adrenergic receptors (β-AR) plays an important role in hippocampal plasticity including the subiculum which is the principal target of CA1 pyramidal cells and which controls information transfer from the hippocampus to other brain regions including the neighboring presubiculum and the entorhinal cortex (EC). Subicular pyramidal cells are classified as regular- and burst-spiking cells. Activation of β-ARs at CA1-subiculum synapses induces long-term potentiation (LTP) in burst- but not in regular-spiking cells (Wojtowicz et al., 2010). To elucidate seizure-associated disturbances in the norepinephrine-dependent modulation of hippocampal output, we investigated the functional consequences of the β-AR-dependent synaptic plasticity at CA1-subiculum synapses for the transfer of hippocampal output to the parahippocampal region in the pilocarpine model of temporal lobe epilepsy. Using single-cell and multi-channel field recordings in slices, we studied β-AR-mediated changes in the functional connectivity between CA1, the subiculum and its target-structures. We confirm that application of the β-adrenergic agonist isoproterenol induces LTP in subicular burst- but not regular-spiking cells. Due to the distinct spatial distribution of regular- and burst-spiking cells in the proximo-to-distal axis of the subiculum, in field recordings, LTP was significantly stronger in the distal than in the proximal subiculum. In pilocarpine-treated animals, β-AR-mediated LTP was strongly reduced in the distal subiculum. The attenuated LTP was associated with a disturbed polysynaptic transmission from the CA1, via the subiculum to the presubiculum, but with a preserved transmission to the medial EC. Our findings suggest that synaptic plasticity may influence target related information flow and that such regulation is disturbed in pilocarpine-treated epileptic rats. Copyright © 2014. Published by Elsevier Ltd.Neuroscience 12/2014; 286. · 3.33 Impact Factor
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ABSTRACT: Brains are dynamic systems, consisting of huge number of massively interconnected elementary components. The activity of these components results in an initial condition-sensitive evolution of network states through highly non-linear, probabilistic interactions. The dynamics of such systems cannot be described merely by studying the behavior of their components; instead their study benefits from employing multimodal methods. Neural-Event-Triggered (NET) fMRI is a novel method allowing identification of events that can be used to examine multi-structure activity in the brain. First results offered insights into the networks that might be involved in memory consolidation. On-going work examines the physiological underpinnings of the up and down modulation of metabolic activity, mapped with this methodology. Copyright © 2014. Published by Elsevier Ltd.Current Opinion in Neurobiology 12/2014; 31C:214-222. · 6.77 Impact Factor