B. J. McCabe

Effects of the novelty or familiarity of visual stimuli on the expression of the immediate early gene c-fos in rat brain

To investigate substrates of recognition memory, the cellular expression of Fos protein in rat brain has been studied after groups of rats were either shown sets of novel or highly familiar objects, or were exposed to the same pattern of illumination without objects being shown. Counts of stained nuclei were made in eight brain regions, where information about novel or familiar visual stimuli is likely to be processed or stored. The counts were relatively high in occipital visual association cortex and area TE of temporal cortex, intermediate in perirhinal cortex, entorhinal cortex, anterior cingulate cortex and the diagonal band of Broca, and low in the hippocampal formation and mediodorsal nucleus of the thalamus. The number of Fos-stained cells was significantly higher for the rats shown novel objects than for those shown familiar objects in perirhinal cortex, area TE, occipital cortex and anterior cingulate cortex. Arguments are advanced that these differences in counts indicate areas involved in the processing and/or storage of information about the novelty or familiarity of visual stimuli, information important to recognition memory.

Effects of restricted lesions of the chick forebrain on the acquisition of filial preferences during imprinting

The effects of placing bilateral lesions in that part of the chick brain (IMHV) which was previously been implicated in imprinting, was studied in young domestic chicks. Twenty-four dark-reared chicks were matched in pairs on the basis of their approach activity during a 30 min period of exposure to one of two visual imprinting stimuli. Both members of the chick pair were then anaesthetized and bilateral lesions were made by radio-frequency coagulation in the IMHV of one chick; the other chick served as a sham-operated control. On the following day each chick was exposed for 2.5 h to the imprinting stimulus to which it had previously been exposed. After training, the preferences of all chicks were measured by comparing their approach to the training stimulus with that to the second stimulus. Sham-operated chicks showed a strong preference for the training stimulus; lesioned chicks showed none. Subsequently the latency of each chick to approach and accurately peck a shiny rod was measured. The two groups of chicks did not differ significantly in this test of visuomotor coordination. The area of tissue damaged by the lesion was reconstructed: IMHV was severely damaged with relatively little damage to other areas of the brain.

Mapping visual recognition memory through expression of the immediate early gene c-fos

To study brain regions involved in familiarity discrimination, rats were shown sets of novel and familiar objects. On each trial two objects were shown simultaneously to a rat so that one eye saw a novel object while the other saw a familiar object. Thus novel and familiar objects were seen with the same conditions of alertness and eye movements. Activated neurones were revealed by staining for products of the immediate early gene c-fos. Familiar stimuli activated significantly fewer neurones than novel stimuli in perirhinal cortex and area TE of temporal cortex, and the ventral lateral geniculate nucleus of the thalamus, but not in the hippocampus or other areas sampled. These findings are discussed in relation to recognition memory.

Hemispheric asymmetry and imprinting: The effect of sequential lesions to the hyperstriatum ventrale

SummaryThe respective roles in the imprinting process of parts (IMHV) of the left and right hyperstriatum ventrale of the chick brain were examined by destroying first one and then the other IMHV in a two-stage operation. One hundred and eight chicks were dark-reared to ≃ 19 h post-hatch and exposed to a training stimulus for 2 h. Chicks were anaesthetised ≃ 3 h after the end of training. Lesions were placed in either (i) right IMHV (N = 18 birds), (ii) left IMHV (N = 18) or (iii) left or right hyperstriatum accessorium (HA; N = 18). Fifty-four chicks served as sham-operated controls. Chicks were returned to the dark incubator, and, 15–20 h after the operation, the chicks’ approach towards the training stimulus and to a second novel stimulus was measured (Test 1). After this test the chicks were again anaesthetised and a second lesion was made, this lesion being placed in the corresponding structure (IMHV or HA) of the hemisphere contralateral to that with the first lesion. The chicks’ preferences were measured 15–20 h later (Test 2). In Test 1, all birds strongly preferred the training stimulus. In Test 2, sham-operated controls and HA chicks continued to prefer the training stimulus as did chicks with the initial lesion in the left IMHV. However, chicks with the initial lesion in the right IMHV failed to show a preference for the training stimulus. Thus, if the right IMHV is destroyed first the presence of the left IMHV is crucial for retention. In contrast, if the left IMHV is destroyed first the presence of the right IMHV is not crucial for retention: chicks continue to prefer the training stimulus after the right IMHV has been lesioned. In these circumstances, therefore, some region outside IMHV takes on a memory function. The results imply that at least two memory systems are formed during imprinting. One of these involves the left IMHV, the other does not. The putative second system is fully able to sustain recall in the normal chicks by ≃ 26 h after training: if bilateral lesions to IMHV (N = 28 chicks) are made at this time, retention, measured 15–20 h later, is not significantly different from that of sham-operated control chicks (N = 25).

Differential activation of the rat hippocampus and perirhinal cortex by novel visual stimuli and a novel environment

Two groups of rats were shown individual novel visual objects. One group had been familiarised to the environmental context within which the objects were shown, the other experienced the situation for the first time. The activation of neurones in perirhinal cortex and the hippocampal formation was determined by counts of nuclei stained for products of the immediate early gene c-fos. The ratio of counts in the hippocampal formation to that in perirhinal cortex was compared for the two groups: the ratio was significantly higher (4.2:1) in the group experiencing the environment for the first time. Thus, whereas perirhinal neurones are activated by novel rather than familiar objects, hippocampal neurones are preferentially activated by a novel rather than a familiar environment.

Amnesic effects of bilateral lesions placed in the hyperstriatum ventrale of the chick after imprinting

SummaryThe purpose of this study was to investigate whether bilateral lesions to a part of the hyperstriatum ventrale (IMHV) impair retention if they are placed after chicks have been imprinted. Domestic chicks were hatched and reared in darkness and exposed to an imprinting (training) stimulus for 2 h commencing ≃ 22 h post hatch. The chicks were then anaesthetised and bilateral lesions placed in IMHV (N = 16) birds, hyperstriatum accessorium (HA; N = 16) or the lateral part of the cerebral hemispheres (LCA; N = 16). Forty-eight sham-operated chicks served as controls. Chicks were returned to the dark incubator, and, 15–20 h after the operation, their approach towards the training stimulus and to a second novel stimulus was measured. The controls and the chicks with lesions in HA and LCA showed a strong preference for the training stimulus and hence a high level of retention. The preferences of these three experimental groups did not differ significantly from one another. The mean preference of chicks with lesions in IMHV was significantly less than that of the sham-operated controls (P<0.01) and of chicks lesioned in HA (P<0.05). Bilateral lesions to IMHV therefore selectively impair retention of a preference acquired through imprinting. This impairment is unlikely to be a non-specific consequence of defective sensory processing or motor performance because the four groups did not differ from each other in (i) the time taken accurately to peck a rocking bead, (ii) the accuracy of pecking millet seeds and (iii) the performance of a simultaneous visual discrimination task involving heat reinforcement.

Synaptic transmission and recognition memory: time course of changes in N-methyl-D-aspartate receptors after imprinting.

Previous studies have shown that a restricted region of the chick forebrain (the intermediate and medial parts of the hyperstriatum ventrale, IMHV) is crucial for the learning process of imprinting. A learning-related increase in N-methyl-D-aspartate (NMDA) receptor binding has previously been shown in the left IMHV 8.5 hr after training with an imprinting stimulus. The present experiments showed that this increase in binding in the left IMHV does not occur until 6-8.5 hr after training: There was no significant change in binding in either the left or right IMHV less than 0.5, 3, or 6 hr after training. No significant change in binding occurred in the right IMHV 8.5 hr after training. It is probable that the increase in binding in the left IMHV is associated with the recognition memory of imprinting.

Noradrenaline and learning: effects of the Noradrenergic neurotoxin DSP4 on imprinting in the domestic chick

The effects of the noradrenergic neurotoxin DSP4 on imprinting in domestic chicks were investigated. Chicks received either DSP4 or distilled water and were trained 60 hr after hatching by exposing them to either a rotating red box or a stuffed jungle fowl. Noradrenaline concentration was determined in Wulst and medial and basal forebrain samples. The medial forebrain sample comprised mainly the intermediate part of the medial hyperstriatum ventrale, a region previously shown to be intimately involved in imprinting. The DSP4 treatment reduced forebrain noradrenaline levels by about 65%. DSP4 profoundly impaired imprinting in box-trained chicks but not in fowl-trained chicks. In box-trained chicks, the strength of imprinting was positively correlated with noradrenaline concentration in both medial and basal forebrain samples. It is suggested on the basis of these and previous studies that some of the neural structures and mechanisms involved in imprinting on the fowl differ from those involved in imprinting on the box.

Dynamics of a Memory Trace: Effects of Sleep on Consolidation

BACKGROUND There is evidence that sleep is important for memory consolidation, but the underlying neuronal changes are not well understood. We studied the effect of sleep modulation on memory and on neuronal activity in a memory system of the domestic chick brain after the learning process of imprinting. Neurons in this system become, through imprinting, selectively responsive to a training (imprinting) stimulus and so possess the properties of a memory trace. RESULTS The proportion of neurons responsive to the training stimulus reaches a maximum the day after training. We demonstrate that sleep is necessary for this maximum to be achieved, that sleep stabilizes the initially unstable, selective responses of neurons to the imprinting stimulus, and that for sleep to be effective, it must occur during a particular period of time after training. During this period, there is a time-dependent increase in EEG activity in the 5-6 Hz band, that is, in the lower range of the theta bandwidth. The effects of sleep disturbance on consolidation cannot be attributed to fatigue or to stress. CONCLUSIONS We establish that long-term trace consolidation requires sleep within a restricted period shortly after learning. Undisturbed sleep is necessary for the stabilization of long-term memory, measured at the behavioral and neuronal levels, and of long-term but not short-term neuronal responsiveness to the training stimulus.

Neural cell adhesion molecules, learning, and memory in the domestic chick

The intermediate and medial hyperstriatum ventrale (IMHV) of the chick forebrain is a site of recognition memory for the learning process of imprinting. The results reported here demonstrate that neural cell adhesion molecules (NCAMs) play a time-dependent role in this recognition memory. Dark-reared chicks were trained, tested, and assigned a preference score as a measure of learning. Chicks with high preference scores were designated good learners and those with lower preference scores, poor learners. Controls were untrained. Tissue was removed, 9.5 hr or 24 hr after training, from the left and right IMHV, hyperstriatum accessorium, and posterior neostriatum. Three major NCAM isoforms (180, 140, and 120 kDa) were assayed. At 24 hr only, there was in left IMHV significantly more NCAM (for each isoform) in good learners than in the other 2 groups, and also a significant correlation between the amounts of NCAM and preference scores for all isoforms; the amount predicted by each regression line at preference score 50 (no learning) did not differ significantly from the mean value for untrained controls. There were no learning-related effects in either the hyperstriatum accessorium or the posterior neostriatum.