Intracellular ATP Influences Synaptic Plasticity in Area CA1 of Rat Hippocampus via Metabolism to Adenosine and Activity-Dependent Activation of Adenosine A(1) Receptors

Stephanie zur Nedden, Simon Hawley, Naomi Pentland, D. Grahame Hardie, Alexander S. Doney, Bruno Frenguelli

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    39 Citations (Scopus)

    Abstract

    The extent to which brain slices reflect the energetic status of the in vivo brain has been a subject of debate. We addressed this issue to investigate the recovery of energetic parameters and adenine nucleotides in rat hippocampal slices and the influence this has on synaptic transmission and plasticity. We show that, although adenine nucleotide levels recover appreciably within 10 min of incubation, it takes 3 h for a full recovery of the energy charge (to >= 0.93) and that incubation of brain slices at 34 degrees C results in a significantly higher ATP/AMP ratio and a threefold lower activity of AMP-activated protein kinase compared with slices incubated at room temperature. Supplementation of artificial CSF with D-ribose and adenine (Rib/Ade) increased the total adenine nucleotide pool of brain slices, which, when corrected for the influence of the dead cut edges, closely approached in vivo values. Rib/Ade did not affect basal synaptic transmission or paired-pulse facilitation but did inhibit long-term potentiation (LTP) induced by tetanic or weak theta-burst stimulation. This decrease in LTP was reversed by strong theta-burst stimulation or antagonizing the inhibitory adenosine A(1) receptor suggesting that the elevated tissue ATP levels had resulted in greater activity-dependent adenosine release during LTP induction. This was confirmed by direct measurement of adenosine release with adenosine biosensors. These observations provide new insight into the recovery of adenine nucleotides after slice preparation, the sources of loss of such compounds in brain slices, the means by which to restore them, and the functional consequences of doing so.

    Original languageEnglish
    Pages (from-to)6221-6234
    Number of pages14
    JournalJournal of Neuroscience
    Volume31
    Issue number16
    DOIs
    Publication statusPublished - 20 Apr 2011

    Keywords

    • LONG-TERM POTENTIATION
    • PROTEIN-COUPLED RECEPTOR
    • IN-VITRO
    • ADENINE-NUCLEOTIDES
    • ENERGY-CHARGE
    • NUCLEOSIDE TRANSPORTER
    • BILATERAL ISCHEMIA
    • SLICE PREPARATIONS
    • CEREBRAL-ISCHEMIA
    • ADENYLATE KINASE

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