Elsevier

Brain Research

Volume 790, Issues 1–2, 20 April 1998, Pages 33-44
Brain Research

Research report
Phasic activation of the locus coeruleus enhances responses of primary sensory cortical neurons to peripheral receptive field stimulation

https://doi.org/10.1016/S0006-8993(98)00117-6Get rights and content

Abstract

In the present study we examined the effects of phasic activation of the nucleus locus coeruleus (LC) on transmission of somatosensory information to the rat cerebral cortex. The rationale for this investigation was based on earlier findings that local microiontophoretic application of the putative LC transmitter, norepinephrine (NE), had facilitating actions on cortical neuronal responses to excitatory and inhibitory synaptic stimuli and more recent microdialysis experiments that have demonstrated increases in cortical levels of NE following phasic or tonic activation of LC. Glass micropipets were used to record the extracellular activity of single neurons in the somatosensory cortex of halothane-anesthetized rats. Somatosensory afferent pathways were activated by threshold level mechanical stimulation of the glabrous skin on the contralateral forepaw. Poststimulus time histograms were used to quantitate cortical neuronal responses before and at various time intervals after preconditioning burst activation of the ipsilateral LC. Excitatory and postexcitatory inhibitory responses to forepaw stimulation were enhanced when preceded by phasic activation of LC at conditioning intervals of 200–500 ms. These effects were anatomically specific in that they were only observed upon stimulation of brainstem sites close to (>150 μm) or within LC and were pharmacologically specific in that they were not consistently observed in animals where the LC-NE system had been disrupted by 6-OHDA pretreatment. Overall, these data suggest that following phasic activation of the LC efferent system, the efficacy of signal transmission through sensory networks in mammalian brain is enhanced.

Introduction

The widespread efferent projection from the nucleus locus coeruleus (LC) to multiple, functionally diverse regions of the mammalian central nervous system is well established [[51] and see Review [14]]. The majority of early studies whose aim was to investigate the potential for this noradrenergic system to influence cell activity in different brain circuits examined the effects of microiontophoretically applied norepinephrine (NE) on spontaneous discharge rates and neuronal responses to synaptic stimuli 2, 15, 16, 19, 43, 50, 56, 57. One target of these investigations was primary sensory circuits where it was shown that constant low level administration of NE could differentially suppress evoked versus spontaneous discharge such that the signal to noise ratio of synaptically mediated responses was increased 15, 55, 56. In many instances NE potentiated responses of sensory cortical neurons to either excitatory or inhibitory synaptic inputs while producing no direct effect on the spontaneous firing rate of these cells [56]. The results of more recent studies have further suggested that iontophoretic NE can alter receptive field properties of primary visual cortical neurons in rat [52] and cat 24, 33. In essence microiontophoretic application of NE under these conditions was intended to mimic tonic release of NE from noradrenergic nerve terminals in local sensory networks. While this approach yielded many new insights into the potential role of the central noradrenergic system in neural circuit operations, it did not fully approximate synaptic release of NE. For example, it is well known that individual NE-containing cells within LC vary their tonic firing rates across the sleep/waking cycle [3] as well as discharge in a phasic burst mode in response to novel or salient sensory stimuli 4, 13. Furthermore, based upon multi-unit electrophysiological recordings 3, 4, it is generally acknowledged that neurons within LC discharge en masse, either tonically or phasically, in response to afferent inputs. Thus, while microiontophoresis provides for continuous local release of NE, activation of the LC efferent pathway would result in simultaneous release of NE, either tonically or phasically, at multiple sites throughout the neuraxis. An important step in establishing the physiological significance of NE's modulatory actions on sensory signal transmission is to determine the extent to which phasic or tonic activation of the LC-noradrenergic pathway can induce NE-like enhancement of stimulus-evoked responses in sensory cortical neurons. With this objective in mind, the goal of the present study was to characterize the effects of phasic activation of LC on responses of somatosensory cortical neurons to tactile stimulation of their peripheral receptive fields.

Section snippets

Materials and methods

Experiments were carried out on 37 Sprague–Dawley female rats weighing 200–300 g. Six of these animals were pretreated with 6-OHDA (see below). Rats were anesthetized with halothane (0.5–0.75% in oxygen), intubated and allowed to breathe spontaneously. Body temperature was monitored by means of a rectal probe and maintained at 36–37°C with a heating lamp. After an animal had been fixed in a stereotaxic frame, a midline incision was made in the scalp, and the skull and dura overlying the

Results

Interactions between phasic activation of brainstem sites in or near LC and neuronal responses to afferent synaptic inputs were studied in 39 cells located in layers V and VI of the forepaw region of rat primary somatosensory cortex. Similar interactions were studied in 25 additional cells recorded from cortical layers V and VI of 6-OHDA treated animals. As reported previously [9], extracellularly recorded unit responses to tactile stimulation of the contralateral forepaw included either 1) a

Discussion

In the present study we showed that phasic activation of LC could enhance both excitatory and inhibitory components of primary somatosensory cortical neuron responses to threshold level tactile stimulation of peripheral receptive fields. Such effects were optimal with condition-test intervals of 100–400 ms and were observed in cells recorded from cerebrocortical layers V and VI. The levels of LC stimulation that were capable of enhancing neuronal responsiveness to synaptic inputs were

Acknowledgements

This work was supported by NIH NS 32461 to BDW. The authors wish to thank Dr. Sam Speciale for HPLC determinations of norepinephrine levels in 6-OHDA treated and sham operated control animals and Dr. John Rutter for helpful comments during preparation of the manuscript for publication.

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  • Cited by (0)

    1

    Department of Physiology, University of Michigan Medical School, Ann Arbor, MI 48109-0622, USA.

    2

    Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27183, USA.

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