Biomedical subjects

Grant R J Gordon

Publications and source records attributed to Grant R J Gordon.

4 recordsLinked to original sources

PubMed2006

Can homeostatic circuits learn and remember?

Alterations in synaptic strength are thought to represent the cellular basis of learning and memory. While such processes appear to be fundamental to all synapses, until recently there has been a relative dearth of information regarding synaptic 'memory' processes in autonomic circuits. Here we examine recent advances in our understanding of plasticity at glutamatergic synapses onto magnocellular neurosecretory cells in the hypothalamus, paying particular attention to the contributions of noradrenaline in coding long-lasting pre- and postsynaptic changes in efficacy. We also highlight recent work demonstrating that glial cells play a crucial role in the induction of long-term potentiation. Based on the work reviewed here, we have a clearer picture of the synaptic and cellular mechanisms that allow autonomic pathways to learn and remember.

Animals↗

PubMed2005

Noradrenaline triggers multivesicular release at glutamatergic synapses in the hypothalamus.

The origin of large-amplitude miniature EPSCs (mEPSCs) at central synapses remains to be firmly established. Here, we show that at excitatory synapses onto magnocellular neurosecretory cells in the hypothalamus, noradrenaline induces a rapid and robust increase in mEPSC amplitude that requires alpha1-adrenoceptor activation but is impervious to postsynaptic manipulations that block the putative insertion of AMPA receptors. In response to noradrenaline, mEPSCs exhibit a putative multimodal amplitude histogram distribution that is not attributable to random temporal summation, the unveiling of a quiescent synapse, or the release of large vesicles. Large-amplitude mEPSCs are sensitive to a high dose of ryanodine and are associated with an enhanced glutamate cleft concentration. Together, these data are consistent with the hypothesis that large-amplitude mEPSCs result from the synchronous release of multiple vesicles via rapid presynaptic calcium expulsion from intracellular stores.

Animals↗

PubMed2005

Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy.

Glial cells actively participate in synaptic transmission. They clear molecules from the synaptic cleft, receive signals from neurons and, in turn, release molecules that can modulate signaling between neuronal elements. Whether glial-derived transmitters can contribute to enduring changes in postsynaptic efficacy, however, remains to be established. In rat hypothalamic paraventricular nucleus, we demonstrate an increase in the amplitude of miniature excitatory postsynaptic currents in response to norepinephrine that requires the release of ATP from glial cells. The increase in quantal efficacy, which likely results from an insertion of AMPA receptors, is secondary to the activation of P2X(7) receptors, an increase in postsynaptic calcium and the activation of phosphatidylinositol 3-kinase. The gliotransmitter ATP, therefore, contributes directly to the regulation of postsynaptic efficacy at glutamatergic synapses in the CNS.

Adenosine Triphosphate↗

PubMed2003

Priming of excitatory synapses by alpha1 adrenoceptor-mediated inhibition of group III metabotropic glutamate receptors.

Adaptive responses mediated by the hypothalamus require sustained activation until homeostasis is achieved. Increases in excitatory drive to the magnocellular neuroendocrine cells that mediate these responses, however, result in the activation of a presynaptic metabotropic glutamate receptor (mGluR) that curtails synaptic excitability. Recent evidence that group III mGluRs can be inhibited by protein kinase C prompted us to test the hypothesis that activation of PKC by noradrenaline (NA) inhibits group III mGluRs and increases excitatory synaptic input to these cells. To examine the effects of NA on miniature EPSCs (mEPSCs), we obtained whole-cell recordings from magnocellular vasopressin and oxytocin neurons in the paraventricular nucleus of the hypothalamus. All of the neurons tested in the current study displayed an alpha1 adrenoceptor-mediated increase in mEPSC frequency in response to NA (1-200 microm). The excitatory effects of NA were mimicked by the phorbol ester PMA and blocked by the PKC inhibitor calphostin C. The activation of PKC inhibits the efficacy of group III mGluRs, resulting in an increase in mEPSC frequency in response to a subsequent exposure to NA. By removing feedback inhibition, this mechanism effectively primes the synapses such that subsequent activation is more efficacious. The novel form of synaptic rescaling afforded by this cross-talk between distinct metabotropic receptors provides a means by which ascending catecholamine inputs can facilitate the control of homeostasis by hypothalamic networks.

Animals↗