Interactions of norepinephrine with Purkinje cell responses to putative amino acid neurotransmitters applied by microiontophoresis

Abstract

In cerebellum, the evoked responses of the Purkinje neuron to both excitatory and inhibitory afferent input are enhanced by local norepinephrine (NE) administration. To determine the nature of this synergistic interaction between NE and the synaptic inputs, Purkinje cell responses to microiontophoretically applied amino acid neurotransmitters were examined before, during, and after NE iontophoresis. NE was found to preferentially augment GABA-induced inhibition, whereas it antagonized inhibition produced by glycine. This enhancement of GABA inhibition was seen at NE doses which caused minimal change in spontaneous activity, and at times after spontaneous discharge returned to control levels following NE application. Dopamine did not facilitate the response to GABA even at doses having direct depressant effects on spontaneous discharge. Glutamate-evoked excitations and subsquent depressions were also augmented during NE administration, relative to the level of background activity. Thus, NE selectively enhanced responses of Purkinje neurons produced by microiontophoretic application of amino acids postulated to be cerebellar neurotransmitters, supporting the hypothesis that NE acts on postsynaptic processes to increase the responsiveness of the Purkinje cell to afferent input. These data also provide evidence supporting the concept that a primary effect of noradrenergic input to cerebellum may be to modulate the action of other transmitters.