Burton M. Slotnick

Rats with low levels of brain docosahexaenoic acid show impaired performance in olfactory-based and spatial learning tasks

Studies were carried out to determine if decreased levels of central nervous system docosahexaenoic acid (DHA), a result of consuming an n-3-deficient diet, had an effect on learning- and memory-related behaviors in adult male rats. Females were reared on an n-3-deficient or n-3-adequate diet beginning at 21 d of life. Their male pups, the F2 generation, were weaned to the diet of the dam and tested at 9–12 wk of age. An olfactory-based discrimination and Morris water maze task were used to assess performance. Whole brain was collected after the behavioral experiments and central nervous system fatty acid content was analyzed in olfactory bulb total lipid extracts. F2 generation male rats consuming the n-3-deficient diet had an 82% decrease in DHA compared to rats consuming the n-3-adequate diet. The n-3-deficient animals made significantly more total errors in a 7-problem, 2-odor discrimination task compared to the n-3-adequate group. Furthermore, the escape latency in the Morris water maze task was significantly longer for the n-3-deficient rats compared to the n-3-adequate rats. These results indicate that rats with decreased DHA levels in the central nervous system perform poorer in these tasks compared to rats with higher DHA levels and suggest the presence of learning deficits in these animals.

Cognitive deficits in docosahexaenoic acid-deficient rats.

This study investigated the influence of brain docosahexaenoic acid (DHA) deficiency on simple and complex olfactory-based learning and memory in 2nd generation (F2) adult male rats. Rats raised and maintained on either an n-3-adequate or an n-3-deficient diet were tested for acquisition of an olfactory learning set and an olfactory memory task, and for motivation to obtain a water reward. Despite a 76% decrease in brain DHA, n-3-deficient rats were able to acquire most simple 2-odor discrimination tasks but were deficient in the acquisition of a 20-problem olfactory learning set. This deficit could not be attributed to changes in sensory capacity but, instead, appeared to represent a deficit in higher order learning.

Disturbances of maternal behavior in the rat following lesions of the cingulate cortex.

Using retrieving and other tests, the maternal behavior of a series of albino rats was tested before and after operative procedures. All lesions were made electrolytically and were stereotaxically placed. Motor acts observed during the behavioral tests included retrieving pups, licking pups, adopting the nursing position over retrieved pups and nest forming activities. Results of the operative procedures indicate that sham operations and ablations of a narrow strip of neocortical tissue lateral to the cingulate cortex do not appreciably alter the normal behavior pattern or interfere with the adequacy of maternal care. Animals with lesions of the anterior and posterior cingulate cortex (resulting in retrograde degeneration in the anterior thalamic nuclei) showed a disruption of these motor patterns including a distinct qualitative change in behavior towards pups. Slow retrieving with frequent pauses for grooming or sniffing about the cage, licking of unretrieved pups and little inclination to nurse pups characterized the behavior of these animals during the retrieving tests. All motor patterns seen in the normal animal were expressed by these rats but often in an irregular and confused manner. Pups would be repeatedly brought into and carried out of the nest site or dropped randomly about the cage. The nursing position would be adopted over one or two pups, in or out of the nest site, while the other pups were ignored. Judging from the relatively short latency of responding to the pups and nesting material and by the excitement evident in their aberrant pup retrieving and nest forming behavior, there seemed to be little or no loss of maternal motivation. The pups and nesting material were adequate stimuli to initiate the various motor acts observed in control animals. This aberrant behavior improved over repeated tests and by the third or fourth postpartum day the confusion seen in the earlier tests was less evident and most behavioral scores were close to the normal range. However, when these animals were tested in a strange, brightly illuminated cage, a thorough disruption of maternal behavior again occurred. Pre- and postpartum injections of prolactin resulted in no improvement. Supplying the animal with a small box with a narrow opening (a nest site preferred by normal animals) was also without effect in reducing the disturbed maternal behavior pattern. Lesions limited to the anterior or posterior cingulate cortex resulted in an intermediate loss which quickly improved during subsequent testing. Loss in maternal behavior in animals with partial and full cingulate lesions were significantly correlated with the severity of retrograde degeneration in the anterior thalamic nuclei. Maternal behavior (pup retrieving) which was induced in castrated male rats by exposing them to 1-3 day old pups each day did not suffer from neocortical lesions, but was disrupted by cingulate cortical lesions. It was concluded that the cingulate cortex in the rat participates in the integration or organization of complex unlearned activities.

Alterations in brain function after loss of docosahexaenoate due to dietary restriction of n-3 fatty acids.

The concentration of the major polyunsaturated fatty acid (PUFA) in brain, docosahexaenoate, may be markedly reduced by two or more generations of dietary restriction of sources of n-3 fatty acids in the diet. Such a deficiency was induced through the feeding of safflower oil as the principal source of essential fatty acids. The reference point for this diet was an n-3 adequate diet to which alpha-linoleate and docosahexaenoate were added through the addition of a small quantity of flax seed or algael oils, respectively. The loss of brain DHA was associated with poorer performance in spatial tasks and an olfactory-cued reversal learning task. No difference could be observed in the hippocampal gross morphology. This study demonstrates the importance of providing a source of n-3 fatty acids during mammalian growth and development.

Olfactory discrimination deficits in n−3 fatty acid-deficient rats

Docosahexaenoic acid (DHA), a long chain n-3 fatty acid, is present in high concentrations in the central nervous system. Although the role that DHA may play in neural function is not well understood, infants fed formulas containing low levels of n-3 fatty acids have decreased visual acuity and neurodevelopmental test scores. The present experiment assessed whether dietary manipulations that decrease the concentration of DHA in the brain interfered with olfactory-based learning. We fed rats a diet that provided adequate n-3 fatty acids or a diet that was deficient in n-3 fatty acids for two generations. The second generation n-3-deficient group had 81% less brain DHA (82% less in olfactory bulb) compared to the n-3-adequate group and made significantly more errors in a series of olfactory-cued, 2-odor discrimination tasks compared to the adequate group. These results suggest that lower levels of central nervous system DHA lead to poorer performance in a series of simple odor discrimination tasks.

Intraspecific fighting in albino mice with septal forebrain lesions

Abstract Male mice with septal lesions showed a dramatic postoperative increase in emotionality characterized by vigorous biting when restrained and exaggerated attempts to escape capture. In tests of intraspecific aggression they showed little or no fighting behavior and were defeated by normal or sham-lesioned controls. Pre-operative winning experience did not ameliorate the deficit in aggressive behavior. These results are contrary to those previously obtained with rats and hamsters and suggest a species-dependent effect of the lesion on aggressive behavior.

What the rat's nose tells the rat's mouth: Long delay aversion conditioning with aqueous odors and potentiation of taste by odors

In Experiment 1, olfactory bulbectomized and control rats were trained using operant conditioning to determine the taste threshold of aqueous amyl acetate. Concentrations below gustatory threshold were used in Experiments 2–5 to compare the effectiveness of odors with various concentrations of saccharin as cues for illness. The results showed the following: (1) The effectiveness of odor and taste was directly related to concentration; (2) the strength of an aversion to a concentration of taste could be matched by an appropriate concentration of an odor; (3) odor was as effective as taste with CS-US delays of 4 h; and (4) an effective odor potentiated an aversion to an otherwise ineffective taste. The results challenge the privileged role accorded tastes in food aversion learning and the manner in which tastes are held to interact with odors according to the sensory-and-gate channeling analysis of potentiation (Rusiniak, Hankins, Garcia, & Brett, 1979).

Disruption of maternal behavior in rats with lesions of the septal area

Abstract Rats given septal lesions prior to mating did not build nests or nurse their pups. During retrieving tests they carried pups about the cage repeatedly and dropped them in scattered locations. Virgin rats induced to be maternal by housing with foster pups showed similar, but less marked, behavioral deficits. Rats administered septal lesions after parturition became hyperresponsive, ceased all maternal behaviors, and cannibalized their pups. The results indicated that the aberrant maternal behaviors shown by rats with septal lesions did not result from alterations in hormonal status. It was concluded that the lesions disrupted the typical pattern or sequence of maternal activities and that the deficits were probably related to an enhancement of response perseveration.

Odor memory and odor learning in rats with lesions of the lateral olfactory tract and mediodorsal thalamic nucleus

Rats with posterior transection of the lateral olfactory tract (LOT), lesions of the mediodorsal thalamic nucleus (MD), or with combined lesions of these structures were tested for retention of a preoperatively learned multiple odor discrimination task, acquisition of 3 simple 2-odor discrimination problems, and reversal of the last problem of the series. Compared to controls, rats with transection of the LOT had no deficits in any task. Those with MD lesions had no deficits in retention but moderate deficits in acquisition of novel odor discriminations and a severe deficit in reversal learning. Rats with combined LOT and MD lesions had no retention of the preoperatively learned task but their performance on the remaining problems was similar to that of rats with only MD lesions. These results suggest that neither the olfactory thalamocortical projections nor those to the periamygdaloid or entorhinal cortex are essential for storage and/or recall of an olfactory procedural memory task. Performance on the postoperative acquisition tests indicate that the thalamocortical but not the limbic olfactory projections play an important role in olfactory discrimination learning.

Olfactory learning and odor memory in the rat

Rats were trained on a series of 9 tasks, each of which required discrimination among 8 different and unique odors. Discrimination accuracy improved across successive problems and, by the end of training, most rats made few errors after their initial exposure to each new odor. Despite the number of stimuli to be discriminated, this acquisition of a learning set was not appreciably different from that demonstrated in an earlier study that used only 2 odors per task. In subsequent retention tests, most rats also showed excellent memory for odors used in prior problems.