Noradrenergic Modulation of Lateral Geniculate Neurons

Michael Andrew Rogawski, Yale University.

This is an Open Access Thesis


The physiological actions of norepinephrine (NE) were examined in the rat dorsal lateral geniculate nucleus (LGNd) using extracellular single cell recording and microiontophoresis. Prolonged, low current iontophoretic applications of NE consistently elicited an increase in the firing rate of LGNd neurons which was delayed in onset and prolonged after cessation of the ejection. Sympathomimetic amines other than NE also activated LGNd neurons with varying degrees of effectiveness. On the basis of the relative potencies of a series of these agonists and the ability of iontophoretically applied (alpha)-antagonists to selectively block the facilitatory action of NE, it is concluded that NE acts via an (alpha)(,1)- ("postsynaptic") adrenoceptor. Systemic administration of the (alpha)-adrenoceptor antagonist WB-4101 also produced a selective blockade of the response to NE. In contrast to NE, serotonin (5-HT) produced a suppression of the firing of LGNd neurons.To examine the effects of NE on evoked activity, identified geniculocortical relay neurons (P-cells) were driven by electrical stimulation of the afferent visual pathway at the level of the optic chiasm. NE caused a marked facilitation of both the short latency (2-4 msec) and the delay (70-230 msec) responses to such stimulation. The (alpha)-adrenoceptor antagonist phentolamine, which by itself had no consistent effect on evoked activity, strongly diminished the response to NE. 5-HT was a powerful depressant of electrically evoked activity; neither phentolamine nor the 5-HT antagonist methysergide antagonized this response. Firing of LGNd units evoked by flashes of light was also facilitated by NE and depressed by 5-HT.When afferent excitation from the retina was eliminated by enucleation of the eyes, many LGNd neurons ceased firing spontaneously. Silent neurons in enucleated animals generally did not respond to NE although the excitatory amino acid glutamate was still highly active. Under these conditions, NE enhanced the excitation produced by glutamate, suggesting that NE increases the general excitability of these neurons and that it acts in a "neuromodulatory" fashion. The (gamma)-aminobutyric acid (GABA) antagonist picrotoxin, unlike NE, did not facilitate the action of glutamate, indicating that the action of NE is not mediated by suppression of adjacent GABAergic interneurons.Electrical stimulation of the locus coeruleus (LC), which contributes a dense noradrenergic innervation to the LGNd, mimicked the activating effect produced by locally applied NE. The response to 10 Hz trains was generally delayed and the increased rate persisted after the stimulation period. This effect was blocked by iontophoretic application or intravenous administration of WB-4101. Silent cells in enucleated animals were not activated by LC stimulation, but, as with iontophoretic NE, LC stimulation did facilitate the excitatory action of glutamate. WB-4101 blocked both the facilitatory actions of LC stimulation and of iontophretic NE.It is concluded that NE, action via an (alpha)(,1)-adrenoceptor, facilitates the excitability of LGNd relay neurons to afferent stimulation. The close similarity between the effects of locally applied NE and stimulation of the LC provided evidence that NE is a transmitter in the coeruleogeniculate pathway. This pathway may serve to modulate the transmission of visual information from the retina to the strate cortex.