Rapid habituation of auditory responses of locus coeruleus cells in anaesthetized and awake rats.

The auditory response of locus coeruleus (LC) neurones evoked by novel tones was investigated in anaesthetized and awake rats. Recording the single unit activity of LC neurones, responses to auditory stimuli are found under anaesthesia as well as in the awake animal. There are three types of LC responses to tone: first and by far the most frequent, a burst of several spikes at onset of the tone; second, a burst at tone offset and lastly, a total inhibition to the tone. All responses present a rapid habituation after the first few presentations of the stimulus. The results support the view that the LC plays a role in mediating responses to environmental changes.

Slow oscillations as a probe of the dynamics of the locus coeruleus-frontal cortex interaction in anesthetized rats.

Multiunit or single unit activity recorded simultaneously from frontal cortex (FC) and locus coeruleus (LC) under ketamine anesthesia revealed that both regions show slow oscillatory activity, together or separately. If, however, both regions are engaged in this oscillatory activity, there is a systematic relationship between their phases with peak LC firing always following FC firing by 200-400 ms. This was confirmed by cross-correlational analyses, which indicated that the two structures temporarily form a resonant system. The FC-LC resonant state is, however, loose enough to remain open to other intrinsic or extrinsic influences, keeping the measured frequencies of oscillations at each site slightly different, as demonstrated by a detailed analysis of the autocorrelograms. An injection of lidocaine at the frontal cortex site, while sharply reducing the prefrontal activity to essentially zero, leads to an increase of the LC activity and to a modification of the shape of the LC autocorrelogram, but does not change appreciably the phase relationship between the activity in the two structures during the diminishing activity in FC.

c-Fos expression in the auditory pathways related to the significance of acoustic signals in rats performing a sensory-motor task.

Neuronal activity was established in the auditory pathways in relation to behavioural response and cognitive information processing during a sensory-motor acoustic learning. Rats were trained in three consecutive phases. The first phase was an association between an auditory stimulus and a food reward; the second phase a simple discrimination between two sounds of different frequency components, and the third phase a more complex discrimination involving both spectral and spatial sound dimensions. Auditory stimuli were bursts of complex sounds lasting 500 ms. Neuronal activity related to the behaviourally relevant stimuli was established in 20 "learning" rats undergoing this protocol, which were progressively sacrificed at the beginning, middle and end of each phase. For comparison, activity was also established in four "control" rats exposed to the same stimuli delivered pseudo-randomly, thus carrying no behavioural meaning. Neuronal activity was assessed immunocytochemically using the functional marker Fos. To establish a baseline, two rats were unexposed to controlled acoustic stimulation ("unstimulated" rats). In the superior olivary complex (SOC), inferior colliculus (IC) and medial geniculate body (MGB), the number of Fos-like immunopositive cells was comparable in "learning" and "control" animals, but higher than in the "unstimulated" rats. In the auditory cortex (AC), most prominently in the secondary area Te2, the number of Fos-like positive cells differed between "learning" and "control" rats, suggesting that the auditory cortical areas may be involved in the encoding of the behavioural significance of the acoustic stimuli.

Preferential induction of fos-like immunoreactivity in granule cells of the cochlear nucleus by acoustic stimulation in behaving rats.

Neuronal activity in the cochlear nucleus was mapped in relation to acoustic stimuli that signalled a sensory-motor response, using Fos-like immunoreactivity. Rats were trained to associate an acoustic stimulus with a reward and then to discriminate between two sounds ('learning' rats; n = 18). The same stimuli carrying no behavioural significance were pseudo-randomly presented to 'control' rats (n = 4) to differentiate stimulus related- from learning related-activity. To establish a baseline, Fos-like immunoreactivity was determined in rats (n = 2) unexposed to acoustic stimulation. The number of Fos-positive cells was significantly increased in the rats exposed to sounds ('learning' and 'control') as compared to the non-stimulated animals. This stimulus related increase of Fos-like activity in the cochlear nucleus was most prominent in a subpopulation of small neurons, whose spatial distribution corresponds to that of the granule cells. There was also an increase in the number of Fos-positive neurons of larger size, but less prominent than for the small cells. Brief exposure to sounds (30 s) was sufficient to induce Fos-like activity.

Inhibitory influence of frontal cortex on locus coeruleus neurons.

The functional influence of the frontal cortex (FC) on the noradrenergic nucleus locus coeruleus (LC) was studied in the rat under ketamine anesthesia. The FC was inactivated by local infusion of lidocaine or ice-cold Ringer's solution while recording neuronal activity simultaneously in FC and LC. Lidocaine produced a transient increase in activity in FC, accompanied by a decrease in LC unit and multiunit activity. This was followed by a total inactivation of FC and a sustained increase in firing rate of LC neurons. Subsequent experiments revealed antidromic responses in the FC when stimulation was applied to the LC region. The antidromic responses in FC were found in a population of neurons (about 8%) restricted to the dorsomedial area, FR2. The results indicate that there is a strong inhibitory influence of FC on the tonic activity of LC neurons. The antidromic responses in FC to stimulation of the LC region suggest that this influence is locally mediated, perhaps through interneurons within the nucleus or neighboring the LC.

Response to novelty and its rapid habituation in locus coeruleus neurons of the freely exploring rat.

Activity of single units of the noradrenergic nucleus locus coeruleus was recorded in rats during active exploration of a novel environment. Novelty was controlled by the placement of objects in given holes in a hole board. The basic protocol included a habituation session in which the holes were empty and an object session in which a novel object was placed in one of the two holes. During the habituation session, when the whole environment was unfamiliar, there was a phasic response the first time the rat visited any hole, which habituated after one visit. During the second session, when one of the holes contained an object, the cell fired when the rat encountered the novel object. There was no response to empty holes in this session. The neuronal response was markedly diminished or entirely absent on the second and subsequent visits to object-containing holes, indicative of rapid habituation. In some rats it was possible to run a second object session, when a new object was introduced into a previously empty hole. Visits to this hole elicited a robust response, which again habituated after one single visit. The results show that the responses of locus coeruleus to novelty or change, which has been demonstrated in formal learning situations, occurs in freely behaving rats while they are learning about a new environment. Moreover, the response to novelty and change in the environment is short-lived, rapidly habituating after one or two encounters with the stimulus.