Noradrenergic potentiation of excitatory transmitter action in cerebrocortical slices: evidence for mediation by an α1 receptor-linked second messenger pathway

Abstract

Considerable evidence from intact, anesthetized preparations suggests that norepinephrine (NE) can modulate the efficacy of synaptic transmission within local circuits of the mammalian neocortex; i.e. both iontophoretic application of NE and activation of the coeruleocortical pathway are capable of facilitating cortical neuronal responses to non-noradrenergic synaptic inputs and putative transmitter agents. In the present study, the effects of NE on somatosensory cortical neuronal responses to putative excitatory transmitters were characterized using in vitro tissue slice preparations. Somatosensory unit responses to iontophoretic pulses of acetylcholine (ACh) or glutamate (Glu) (10-60 nA; 5-25 s duration) were examined before, during and after a period of continuous NE (1-35 nA; 4-25 min duration) microiontophoresis. Quantitative analysis of per-event histograms indicated that both Glu- and ACh-evoked excitatory discharges were routinely (Glu 94%, n = 54; ACh 67%, n = 9) potentiated above control levels during NE administration. In 8 cells, NE revealed robust excitatory discharges to otherwise subthreshold iontophoretic doses of Glu. The alpha-specific agonist, phenylephrine, mimicked (n = 3), NE-induced potentiation of Glu-evoked discharges whereas the alpha antagonist phentolamine blocked (n = 5) enhancement of these responses. Moreover, activation of protein kinase C by iontophoretic application of phorbol 12,13-diacetate (5-15 nA, n = 4) mimicked the potentiating actions…