Elizabeth D. Abercrombie

Caudate unit activity in freely moving cats: effects of phasic auditory and visual stimuli

The effects of phasic auditory or visual stimuli upon the single unit activity of serotonergic neurons within the dorsal raphe nucleus (DRN) were studied in freely moving cats. The predominant response to auditory stimulation (86% of the cells) was excitation, with a mean latency of 40 +/- 3 ms (S.E.M.) and a mean duration of 64 +/- 4 ms. This was typically followed by a longer period (206 +/- 32 ms) with unit activity below the baseline level. This did not appear to be a stimulus-induced inhibition of unit activity, however, since its duration closely corresponded to the normal interspike interval for that particular neuron. The response to repetitive auditory stimulation showed no evidence of habituation and was even present during sleep. A similar response, although generally of lesser magnitude, was evoked by a phasic visual stimulation in 64% of the cells tested. The mean latency for the response to visual stimulation was 53 +/- 4 ms, the mean duration of excitation was 76 +/- 7 ms, and the mean duration of the subsequent suppressed period was 239 +/- 37 ms. The response to the visual stimulus also showed no evidence of habituation. These data indicate that serotonergic neurons of the DRN are driven, with similar temporal characteristics, by stimuli in two different sensory modalities. We hypothesize that these similar effects are attributable to a common excitatory input.

Systemic naloxone administration potentiates locus coeruleus noradrenergic neuronal activity under stressful but not non-stressful conditions

When administered during non-stressful, quiet-waking conditions, i.v. naloxone (1.0 mg/kg) had no effect on the activity of locus coeruleus (LC) noradrenergic neurons in behaving cats. In contrast, the activation of LC noradrenergic unit activity produced by restraint stress was greatly potentiated by the same dose of naloxone. Indices of behavioral distress, vocalization and struggling, were also found to be significantly increased in animals given naloxone during stress. These results suggest that endogenous opioids have a moderating influence upon the level of activity of the LC which operates only under specific conditions such as stress.

Single-unit and physiological analyses of brain norepinephrine function in behaving animals.

In behaving cats, the single-unit activity of locus coeruleus noradrenergic neurons is strongly activated by a variety of challenges (stressors). For example, exposing cats to a dog or to loud white noise, dramatically increases the activity of these neurons and simultaneously produces strong activation of the sympathetic nervous system. Similarly, glucoregulatory, thermoregulatory, and cardiovascular challenges also coactivate noradrenergic neurons and the sympathetic nervous system. A related research program utilized a simple brainstem response (the monosynaptic jaw closure reflex) to explore the physiological significance of this response of brain noradrenergic neurons. Conditions which activate these neurons were also shown to potentiate the elicited jaw closure-reflex response. Importantly, when the noradrenergic input to the motor side of this reflex pathway was destroyed with a neurotoxin, the conditions which previously potentiated the reflex were now ineffective. These data represent the first demonstration that the release of norepinephrine, at a specific site, and under physiological conditions, facilitates behavioral output in the intact organism.

Microinjected clonidine inhibits noradrenergic neurons of the locus coeruleus in freely moving cats

Microinjection of the alpha 2-adrenoceptor agonist, clonidine (CLON; 1.0 microgram/0.1 microliter) effected a virtually complete suppression of the spontaneous activity of noradrenergic neurons of the locus coeruleus in freely moving cats. This effect lasted for approximately 90 min and was reversible by systemic administration of the alpha 2-adrenoceptor antagonist, yohimbine. In contrast, CLON had no consistent effect on the activity of neighboring non-noradrenergic neurons. These results provide additional evidence for the direct inhibition of central noradrenergic neurons by CLON by demonstrating such effects independent of anesthesia or the behavioral effects of systemic drug administration. More generally, these findings demonstrate the usefulness of a technique in which small amounts of drug can be applied in small volumes to produce a neuropharmacologically specific effect upon locally recorded neurons in behaving animals.

Dopaminergic modulation of sensory responses of striatal neurons: single unit studies

The extracellular single unit responses of striatal neurons to repetitive stimulation of the sciatic nerve were recorded in the urethane anesthetized rat. Changes in the magnitude of these responses after pharmacological manipulation of dopamine (DA) neurotransmission were evaluated. While the intravenous administration of 0.25 mg/kg i.v. amphetamine (AMPH) had no significant effect on baseline firing rates as compared to saline controls, the magnitudes of excitatory and inhibitory evoked single unit responses were significantly decreased by 68% by AMPH. Further, this reduction in response magnitude produced by AMPH was completely blocked by pretreatment with 0.5 mg/kg i.v. haloperidol or by intrastriatal 6-hydroxydopamine lesions. This indicates that the observed effect is mediated by dopamine located in nerve terminals within the striatum. These results suggest that DA functions to modulate the responsiveness of striatal neurons to afferent signals.

Microinjected morphine suppresses the activity of locus coeruleus noradrenergic neurons in freely moving cats

Microinjection of morphine (1.0 microgram/0.1 microliter) produced a significant suppression (approximately 60%) of the single unit activity of locus coeruleus noradrenergic neurons in freely moving cats. This effect was reversible by systemic administration of the opioid receptor antagonist, naloxone (1.0 mg/kg i.v.). The microinjection of naloxone (1.0 microgram/0.1 microliter), however, was without effect on the spontaneous activity of noradrenergic neurons in the locus coeruleus. Non-noradrenergic neurons recorded in the same vicinity showed no consistent response to the microinjection of morphine. These results suggest that the direct effect of opioids in the locus coeruleus is an inhibition of noradrenergic neuronal activity. Furthermore, it appears that opioid influences upon these neurons are not tonically active.

Effect of buspirone on single unit activity in locus coeruleus and dorsal raphe nucleus in behaving cats

The effects of administration of the non-benzodiazepine anxiolytic buspirone on the spontaneous and sensory evoked single unit activity of serotonergic (5-HT) neurons in the dorsal raphe nucleus and noradrenergic (NE) neurons in the locus coeruleus were examined in freely moving cats. Buspirone (1.0 mg/kg i.p.) strongly suppressed both the spontaneous and evoked activity of 5-HT dorsal raphe nucleus neurons. The spontaneous activity of NE neurons in the locus coeruleus was non-significantly increased by drug administration, while the evoked response was unaffected. These effects occurred during a period of mild behavioral activation. It is suggested that the anxiolytic effects of buspirone administration are not achieved through an action of NE neurons, but may be mediated in part by actions on 5-HT neurons in the dorsal raphe.