RT Journal Article
SR Electronic
T1 Insulin-Like Growth Factor-1 Inhibits Adult Supraoptic Neurons via Complementary Modulation of Mechanoreceptors and Glycine Receptors
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 2267
OP 2276
DO 10.1523/JNEUROSCI.4053-04.2005
VO 25
IS 9
A1 Jeanne Ster
A1 Claude Colomer
A1 Cécile Monzo
A1 Anne Duvoid-Guillou
A1 Françoise Moos
A1 Gérard Alonso
A1 Nicolas Hussy
YR 2005
UL http://www.jneurosci.org/content/25/9/2267.abstract
AB In the CNS, insulin-like growth factor-1 (IGF-1) is mainly known for its trophic effect both during development and in adulthood. Here, we show than in adult rat supraoptic nucleus (SON), IGF-1 receptor immunoreactivity is present in neurons, whereas IGF-1 immunoreactivity is found principally in astrocytes and more moderately in neurons. In vivo application of IGF-1 within the SON acutely inhibits the activity of both vasopressin and oxytocin neurons, the two populations of SON neuroendocrine cells. Recordings of acutely isolated SON neurons showed that this inhibition occurs through two rapid and reversible mechanisms, both involving the neuronal IGF-1 receptor but different intracellular messengers. IGF-1 inhibits Gd3+-sensitive and osmosensitive mechanoreceptor cation current via phosphatidylinositol-3 (PI3) kinase activation. IGF-1 also potentiates taurine-activated glycine receptor (GlyR) Cl- currents by increasing the agonist sensitivity through a extremely rapid (within a second) PI3 kinase-independent mechanism. Both mechanoreceptor channels and GlyR, which form the excitatory and inhibitory components of SON neuron osmosensitivity, are active at rest, and their respective inhibition and potentiation will both be inhibitory, leading to strong decrease in neuronal activity. It will be of interest to determine whether IGF-1 is released by neurons, thus participating in an inhibitory autocontrol, or astrocytes, then joining the growing family of glia-to-neuron transmitters that modulate neuronal and synaptic activity. Through the opposite and complementary acute regulation of mechanoreceptors and GlyR, IGF-1 appears as a new important neuromodulator in the adult CNS, participating in the complex integration of neural messages that regulates the level of neuronal excitability.