Modulation of hippocampal sharp wave-ripple activity in vitro

Sharp wave-ripple-complexes (SPW-Rs) in the intact rodent hippocampus are characterized by slow field potential transients superimposed by ~200 Hz ripple oscillations. Similar events have been recorded in hippocampal slices where SPW-Rs occur spontaneously or can be induced by repeated application of high frequency stimulation (HFS), a standard protocol for induction of long- term potentiation (LTP). SPW-Rs are thought to be involved in memory consolidation process in which transiently stored information is transferred from the hippocampus into the cortical mantle. We used rat hippocampal slices to investigate neuromodulatory effects of the systemic neuromodulator norepinephrine (NE), of the cholinergic agonist nicotine and of the local neuromodulator CNP on stimulus-induced SPW-Rs in the CA3 and CA1. NE dosedependently and reversibly suppressed the generation of SPW-Rs via activation of α1 adrenoreceptors (ARs), as indicated by effects of α AR agonist phenylephrine and preserved effect of NE in presence of the β−AR antagonist propranolol. In contrast, activation of β1 ARs by dobutamine significantly increased the incidence of SPW-Rs and facilitated induction of both LTP and SPW-Rs within the CA3 network. Suppression of SPW-Rs by NE was linked to presynaptic modulation of transmitter release via α1 ARs-mediated reduction in presynaptic Ca2+ uptake. Nicotine, in moderate doses, facilitated expression and induction of SPW-Rs and transformed them into REDs at high concentration. This transition was associated with reduced inhibitory conductance in CA3 pyramidal cells, and this effect was mimicked by administration of low concentrations of bicuculline (1-3 μM). CNP reduced the expression of SPW-Rs in area CA3 and CA1. NE, nicotine and CNP, by modulating hippocampal SPW-Rs, may play a pivotal role in formation of hippocampal- dependent cognitive functions. NE-mediated abrupt and sudden suppression of SPW-Rs might be crucial for switching between behaviors related network states in hippocampus and therefore allow different modes of information processing. In addition, NE by facilitating the induction of hippocampal synaptic plasticity via β ARs may play a crucial role in formation of memory.

Author dc:creator

• Haq, Rizwan ul

• hippocampus
• sharp wave ripples
• norepinephrine
• nicotine
• CNP
• transmitter release

Licence dc:rights.uri

• http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen

Language dc:language

eng

Identifier URI

http://dx.doi.org/10.17169/refubium-15124

OAI record oai:identifier

https://refubium.fu-berlin.de/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Arefubium.fu-berlin.de%3Afub188%2F10926