Brain Research 887 2000 293–300 www.elsevier.com locate bres
Research report
Spontaneous and auditory-evoked activity of medial agranular cortex as a function of arousal state in the freely moving rat: interaction with
locus coeruleus activity
a,b , a
a
Toshikazu Shinba , Laurent Briois , Susan J. Sara
a
´ Neuromodulation et Processus Cognitifs
, Institut des Neurosciences, Universite PM Curie, 9 quai Saint-Bernard 75005 Paris, France
b
Department of Neurophysiology , Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan
Accepted 19 September 2000
Abstract
To characterize the electrophysiological properties of neurons in the medial agranular frontal cortex Fr2 with respect to arousal level and locus coeruleus LC activity, we recorded spontaneous and auditory-evoked single unit activity in these areas simultaneously during
different states of arousal in the rat. In the low-arousal state, as determined by EEG, 14 56 Fr2 neurons showed a tonic increase in spontaneous firing rate and 9 56 presented a clear inhibitory response to tone onset latency 37 ms, duration 200 ms. The inhibitory
response was not clear during the high-arousal state. Cross-correlation analysis of pairs of Fr2 and LC units, excluding activity during the actual tone, also showed a negative correlation from 120 ms before, to 170 ms after, Fr2 discharge in 5 63 pairs, only during low arousal.
Significantly, 4 5 of the Fr2 neurons having this negative correlation with LC were included in that population which showed a tonic increase in spontaneous firing rate and inhibited to tone during low arousal. LC neurons, on the other hand, all showed excitation to tone
stimulation peak latency 30 ms, and response amplitude was not affected by changes in arousal level. The negative correlation in spontaneous activity, as well as their differential responses to tone, suggests an interaction between a select population of Fr2 neurons and
the LC during the low-arousal state. Future studies with lesion or pharmacological manipulations would be necessary to confirm the presence of this interaction.
2000 Elsevier Science B.V. All rights reserved.
Theme : Neural basis of behaviour
Topic : Monoamines and behaviour
Keywords : Medial agranular frontal cortex; Locus coeruleus; Rat; EEG; Arousal; Auditory stimulation
1. Introduction properties of Fr2 neurons in awake animals, with the
exception of studies by Pirch et al. [14,18] showing both Anatomical studies have suggested that the medial
excitatory and inhibitory conditioned responses in this agranular frontal cortex Fr2 of the rat contains the
region in awake rats. Based on these observations, it has homologue of the primate frontal eye field with extensive
been proposed that the Fr2 is a frontal association cortex of cortico-cortical connections [16,17] and subcortical projec-
the rat and is engaged in cognitive functions including tions to brain stem visuomotor centers [23]. Lesion studies
attention. show that unilateral damage of Fr2 in the rat is followed
The locus coeruleus LC is a brain stem noradrenergic by neglect of the contralateral side [8] and appearance of
nucleus that is also involved in attention [1,27] with ipsilateral response bias in a spatial reaction-time task [4].
diffuse projection to widely-distributed areas of the brain There are relatively few studies on electrophysiological
[24]. Administration of drugs which inhibit LC activity or impair noradrenergic function such as clonidine and 6-
hydroxydopamine produces a decrease in novelty-seeking
Corresponding author. Present address: Dept. of Neurophysiology,
behavior and electrodermal response to orienting stimuli
Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo
indicating the disturbance of attention [22,26]. Electro-
156-8585, Japan. Tel.: 181-3-3304-5701; fax: 181-3-3329-8035. E-mail address
: shinbaprit.go.jp T. Shinba.
physiologically, LC neurons show an increase in firing
0006-8993 00 – see front matter
2000 Elsevier Science B.V. All rights reserved. P I I : S 0 0 0 6 - 8 9 9 3 0 0 0 3 0 0 9 - 2
294 T
when arousal level is elevated [1], and are activated in a and each full rotation of the screw advanced the electrode
burst in response to sensory stimuli when they are novel 400 mm. During the recording sessions, the electrode was
[21] or task-relevant [2,20,25]. moved by increments of 50 mm to find a stable unit firing
Luppi et al. [10] have revealed by anatomical tracing activity.
methods that the Fr2 is a cortical afferent to LC in the rat. Two stainless microelectrodes attached to the micro-
Furthermore, the Fr2 is the only region, among multiple drive apparatus were implanted in the Fr2 Bregma 13.0,
frontal areas investigated, that is antidromically activated L 1.25–1.5 and in the LC Lambda 23.9, L 1.15,
by LC stimulation [19]. Suppression of neuronal activity in respectively. The electrode tip in the Fr2 was set at the
the Fr2 increases LC firing in anesthetized rats [19] and surface of the cortex. The LC electrode was lowered to a
electrical stimulation of Fr2 elicits excitatory, inhibitory or depth of 5.0–6.0 mm from the cerebellar surface, and was
mixed excitatory-inhibitory responses in LC [3,7,12]. held at the depth where the recorded cells were identified
These studies suggest a functional relationship between as of LC with the following criteria: localization just below
Fr2 and LC and this might be involved in modulation of the fourth ventricle, situation just medial to the mesence-
attention. Simultaneous recording of unit activity in the phalic trigeminal cells that respond to jaw movement, low
two regions allows further evaluation of this functional spontaneous discharge below 2 Hz during surgery under
relationship through analysis of correlation in the neuronal anesthesia, broad spikes above 0.7 ms, biphasic excitat-
activity. In anesthetized rats, correlative activity between ory–inhibitory response to paw pinch [5]. At the end of
the Fr2 and LC has already been described using single each experiment, the recording site was confirmed his-
unit recording [19]. Further analysis of these data by tologically by passing current through the electrode Fig.
cross-correlograms revealed a consistent phase difference 1A. The alpha 2 receptor agonist, clonidine 15 mg kg,
between the Fr2 and LC activity [9]. However, the i.p. was injected following some LC recording sessions to
presence of slow oscillations, perhaps induced by anes- thesia, limits the functional interpretation of these data.
The present study, therefore, was designed to investigate the interaction between spontaneous Fr2 and LC neuronal
activity in the awake, freely-moving rat, as well as to compare the electrophysiological properties of Fr2 neurons
to LC neurons in response to sensory stimulation during different states of arousal or attention.
2. Materials and methods
