Norepinephrine increases rat mitral cell excitatory responses to weak olfactory nerve input via alpha-1 receptors in vitro

doi:10.1016/S0306-4522(98)00437-0

Neuroscience

Volume 90, Issue 2, 22 February 1999, Pages 595-606

https://doi.org/10.1016/S0306-4522(98)00437-0 Get rights and content

Abstract

A rat olfactory bulb in vitro slice preparation was used to investigate the actions of norepinephrine on spontaneous and afferent (olfactory nerve) evoked activity of mitral cells. Single olfactory nerve shocks elicited a characteristic mitral cell response consisting of distinct, early and late spiking components separated by a brief inhibitory epoch. Bath-applied norepinephrine (1 μM) increased the early spiking component elicited by perithreshold (79% increase, P<0.02), but not by suprathreshold (3% decrease, P>0.05), intensity olfactory nerve shocks. The facilitatory effect of norepinephrine was due to a reduction in the incidence of response failures to perithreshold intensity shocks. Norepinephrine also decreased the inhibitory epoch separating the early and late spiking components by 44% (P<0.05). By contrast, norepinephrine had no consistent effect on the spontaneous discharge rate of the mitral cells. The effects of norepinephrine were mimicked by the α1 receptor agonist phenylephrine (1 μM, P<0.001). Both norepinephrine and phenylephrine modulation of mitral cell responses were blocked by the α1 adrenergic antagonist WB-4101 (1 μM). These findings are consistent with observations that the main olfactory bulb exhibits the highest density of α1 receptors in the brain. The α2 receptor agonist clonidine (100 nM) and the β receptor agonist isoproterenol (1 μM) had inconsistent effects on mitral cell spontaneous and olfactory nerve-evoked activity.

These results indicate that norepinephrine increases mitral cell excitatory responses to weak but not strong olfactory nerve inputs in vitro via activation of α1 receptors. This is consistent with recent findings in vivo that synaptically released norepinephrine preferentially increases mitral cell excitatory responses to weak olfactory nerve inputs. Taken together, these results suggest that the release of norepinephrine in the olfactory bulb may increase the sensitivity of mitral cells to weak odors. Olfactory cues evoke norepinephrine release in the main olfactory bulb, and norepinephrine plays important roles in early olfactory learning and reproductive/maternal behaviors. By increasing mitral cell responses to olfactory nerve input, norepinephrine may play a critical role in modulating olfactory function, including formation and/or recall of specific olfactory memories.

Section snippets

Slice preparation

Experimental procedures were conducted so as to minimize animal suffering, the number of animals used and to utilize alternatives to in vivo techniques. The following procedures were approved by the animal welfare committee of the University of Maryland. Juvenile (22–28-day-old, 70–120 g), male Sprague–Dawley (Zivic Miller) rats were deeply anesthetized with chloral hydrate (400 mg/kg, i.p.) and perfused transcardially for 1–2 min with ice-cold, zero Ca²⁺ artificial cerebrospinal fluid (ACSF;

Results

Recordings were obtained from 49 mitral cells in 45 slices from 36 animals.

Discussion

The major finding of this study is that NE increases the early excitatory spiking component in mitral cells elicited by relatively weak intensity ON shocks in vitro. This action of NE is specific for weak to moderate ON inputs, as responses to strong stimulation were unaffected by NE. The facilitatory action of NE is mainly due to a reduction in the rate of response failures to perithreshold intensity ON shocks. The effect of NE appears to be mediated primarily by α1 receptors as it was: (i)

Conclusions

The present study shows that NE and the α1 receptor agonist phenylephrine increase the early mitral cell spiking response evoked by weak to moderate strength ON shocks. The facilitatory effect of NE occurred in the absence of changes in spontaneous activity and was due to a reduction in the incidence of response failures to perithreshold intensity shocks. These effects are identical to those of synaptically released NE in vivo and are consistent with NE-induced, α1 receptor-mediated

Acknowledgements

This work was supported PHS grants DC03195, DC02588, NS36940 and NS24698.

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Norepinephrine increases rat mitral cell excitatory responses to weak olfactory nerve input via alpha-1 receptors in vitro

Abstract

Section snippets

Slice preparation

Results

Discussion

Conclusions

Acknowledgements

Modulation of a transient outward current in serotonergic neurones by α1-adrenoceptors

Nature

Glomerular synaptic responses to olfactory nerve input in rat olfactory bulb slices

Neuroscience

Norepinephrine-containing locus coeruleus neurons in behaving rats exhibit pronounced responses to non-noxious environmental stimuli

J. Neurosci.

Excitatory actions of norepinephrine on multiple classes of hippocampal CA1 interneurons

J. Neurosci.

Electrically-evoked release of norepinephrine in the rat cerebellum: an in vivo electrochemical and electrophysiological study

Brain Res.

Olfactory recognition: a simple memory system

Science

Enhanced neural response to familiar olfactory cues

Science

Distribution of α1A adrenergic receptor mRNA in the rat brain visualized by in situ hybridization

J. comp. Neurol.

Olfactory nerve stimulation activates rat mitral cells via NMDA and non-NMDA receptors in vitro

NeuroReport

Catecholamine innervation on the basal forebrain. III. Olfactory bulb, anterior olfactory nuclei, olfactory tubercle and piriform cortex

J. comp. Neurol.

Evidence of facilitatory coerulospinal action in lumbar motoneurons of cats

Brain Res.

K+ channel regulation of signal propogation in dendrites of hippocampal pyramidal neurons

Nature

Noradrenergic modulation of dendrodendritic inhibition in the olfactory bulb

Nature

Activation of locus coeruleus enhances the responses of olfactory bulb mitral cells to weak olfactory nerve input

J. Neurosci.

The effect of microinfusions of drugs into the accessory olfactory block to pregnancy

Neuroscience

Neural basis of olfactory memory in the context of pregnancy block

Neuroscience

Changes in the sensory processing of olfactory signals induced by birth in sheep

Science

Serotonergic facilitation of facial motoneurone excitation

Brain Res.

Cellular mechanisms underlying cholinergic and noradrenergic modulation of neuronal firing mode in the cat and guinea pig dorsal lateral geniculate nucleus

J. Neurosci.

Noradrenergic modulation of firing pattern in guinea pig and cat thalamic neurons, in vitro

J. Neurophysiol.

Expression of multiple alpha adrenergic receptor subtype messenger RNAs in the adult rat brain

Neuroscience

Chemoanatomical organization of the noradrenergic input from locus coeruleus to the olfactory bulb of the adult rat

J. comp. Neurol.

The pharmacology of inhibition of mitral cells in the olfactory bulb

Brain Res.

A study of the effects of noradrenaline in the rat olfactory bulb using evoked field potential response

Brain Res.

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

Brain Res.

Modulation of a transient outward current in serotonergic neurones by α₁-adrenoceptors

Distribution of α_1A adrenergic receptor mRNA in the rat brain visualized by in situ hybridization

K⁺ channel regulation of signal propogation in dendrites of hippocampal pyramidal neurons