Research reportPhasic activation of the locus coeruleus enhances responses of primary sensory cortical neurons to peripheral receptive field stimulation
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.
References (57)
- et al.
Brain aminergic axons exhibit marked variability in conduction velocity
Brain Res.
(1980) - et al.
Noradrenergic neurons of the locus coeruleus: inhibition by epinephrine and activation by the alpha-antagonist piperoxane
Brain Res.
(1976) - et al.
Differences in cutaneous sensory response properties of single somatosensory cortical neurons in awake and halothane anesthetized rats
Brain Res. Bull.
(1981) - et al.
Locus coeruleus-induced inhibition of dorsal cochlear nucleus neurons in comparison with lateral vestibular nucleus neurons
Brain Res.
(1980) Control of the neuronal receptive field in somatosensory cortex
Prog. Neurobiol.
(1978)- et al.
Enhanced norepinephrine release in prefrontal cortex with burst stimulation of the locus coeruleus
Brain Res.
(1996) - et al.
Effects of putative neurotransmitters on neuronal activity in monkey auditory cortex
Brain Res.
(1975) - et al.
Interaction of norepinephrine with cerebellar activity evoked by mossy and climbing fibers
Exp. Neurol.
(1977) - et al.
The locus coeruleus in the rat: an immunohistochemical delineation
Neuroscience
(1980) - et al.
Organization of motor and somatosensory neocortex in the albino rat
Brain Res.
(1974)
Studies on norepinephrine-containing afferents of Purkinje cells of rat cerebellum: II. Sensitivity of Purkinje cells to norepinephrine and related substances administered by microiontophoresis
Brain Res.
Spontaneous discharge of Purkinje neurons after destruction of catecholamine-containing afferents by 6-hydroxydopamine
Brain Res.
Activation of the noradrenergic projection from locus coeruleus reduces the excitatory responses of anterior cingulate cortical neurones to substance P
Neuroscience
Effects of locus coeruleus stimulation on neuronal activities of dorsal lateral geniculate nucleus and perigeniculate reticular nucleus of the rat
Neuroscience
A biochemical and morphological study of the altered growth pattern of central catecholamine neurons following 6-hydroxydopamine
Brain Res.
Noradrenaline neuron innervation of the neocortex in the rat
Brain Res.
The organization of brainstem catecholamine innervation tin the rat
Brain Res.
Locus coeruleus projections to cortex: topography and collateralization
Brain Res. Bull.
Noradrenergic modulation of cat area 17 neuronal responses to moving visual stimuli
Brain Res.
Locus coeruleus stimulation potentiates Purkinje cell responses to afferent input: the climbing fiber system
Brain Res.
Locus coeruleus stimulation potentiates local inhibitory processes in rat cerebellum
Brain Res. Bull.
Influence of norepinephrine-containing neurons derived from the locus coeruleus on lateral geniculate neuronal activities of cats
Brain Res.
Some of the electrophysiological and pharmacological properties of the cortical, noradrenergic projection of the locus coeruleus in the rat
Brain Res.
Locus coeruleus activity in monkey: phasic and tonic changes are associated with altered vigilance
Brain Res. Bull.
Modulation of rat cortical area 17 neuronal responses to moving visual stimuli during norepinephrine and serotonin microiontophoresis
Brain Res.
Noradrenergic modulation of somatosensory cortical neuronal responses to iontophoretically applied putative neurotransmitters
Exp. Neurol.
Interaction of norepinephrine with cerebrocortical activity evoked by stimulation of somatosensory afferent pathways in the rat
Exp. Neurol.
Partial injury to central noradrenergic neurons: reduction of tissue norepinephrine content is greater than reduction of extracellular norepinephrine measured by microdialysis
J. Neurosci.
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.