A morphological study of male rat cerebral cortical asymmetry

Reports of morphologic asymmetry in the mammalian brain are becoming the rule rather than the exception. In a previous publication we noted that in the male Long-Evans rat the right cerebral cortex was generally thicker than the left cortex in all nine areas measured. In the present study, in the majority of cortical areas measured, the right hemisphere was also found to be thicker than the left in the S₁ strain of rats for four age groups and under three experimental conditions. The ages at the commencement and termination of exposure to enriched, standard colony, and impoverished conditions were 25 to 55, 60 to 64, 60 to 90, and 25 to 105 days. In some areas the magnitude of the hemispheric asymmetry varied across the different age groups. The environmental conditions affected the degree of right-left difference in one cortical region, medial area 10.     

Aging and environmental influences on two types of dendritic spines in the rat occipital cortex

The density of dendritic spines was determined by counting spines on 34-μm segments from basal branches of pyramidal cells in layers II and III of the rat occipital cortex. Counts began at the first bifurcation site from the soma, and one segment from each side of the neuron was studied. The results of this investigation indicated a marked decrease in spines with a lollipop (type L) configuration from 90 to 414 days of age. After this decrease, the density of type L spines increased to 630 days to the same density as they were at 90 days. The presence or absence of type L spines was not affected by housing the animals in an enriched environment. In contrast to the type L spines, another type of spine, those with a nubbin configuration (type N) increased in density at each age. The density of these type N spines also appeared subject to environmental influences in the oldest group. We conclude that type L spines, after decreasing to the adult level, increase as the animal approaches senescence perhaps as a compensatory mechanism. On the other hand, type N spines increase with age and are responsive to the environment in the old animals. Type N spines possibly represent degenerating spines.     

A golgi study of dendritic morphology in the occipital cortex of socially reared aged rats

The possible role of the environment in the morphology of the aged brain has been previously discussed in a number of studies. This study used rats which were aged in social rather than in isolated environments. The density of basal dendrites from superficial pyramidal cells from the occipital cortex was analyzed utilizing the concentric circle method and the specific ordering of the dendrites quantified with the centripetal ordering system. There were dramatic increases in the density of dendrites in three defined ranges from the soma (50 to 100, 100 to 150, and 150 to 200 μm) from 414 to 630 days of age. The only range that did not increase in density was the soma to 50-μm range. The increase in density was due to increases in both terminal and intermediate segments. These findings suggest that the living conditions of the animal during aging play a role in the appearance of the cortical structure. This study also introduces the separate quantification of branchless segments of dendrites, which were found on 75% of the neurons studied at both 414 and 444 days of age. On the other hand, in both the 90- and the 630-day-old groups, only 33% of the neurons had branchless segments. We suggest that branchless segments may be dying segments in a state of retraction.     

Increased length of terminal dendritic segments in old adult rats' somatosensory cortex: An environmentally induced response

In a previous study we reported longer lengths of terminal dendritic segments of superficial pyramidal neurons in the rat visual cortex for neurons from 630-day-old animals that had been exposed to enriched environments. The present investigation extends that finding to the somatosensory cortex.     

A Golgi study of the superficial pyramidal cells in the somatosensory cortex of socially reared old adult rats

Following a series of investigations into the appearance of the basal dendritic skirt of pyramidal cells in the supragranular layers of the occipital cortex of the aged rat, we now extend our findings to the somatosensory cortex of these same animals. Specifically, the total number of dendritic branches increased from 414 to 630 days of age due primarily to an increase in third and sixth order branches. The total number of branchless segments which we have suggested may be a vestige of a portion of the dendritic tree was greater in the 414-day-old group than in the 630-day-old group. The dendritic density was also measured in four specific ranges from the soma (0 to 50 μm, 50 to 100 μm, 100 to 150 μm, 150 to 200 μm). Only the 50 to 100-μm range did not show an increase in density with age. By utilizing an orientation factor in the concentric circle analysis, the increase in dendritic density for the range nearest the soma was found to be only in the upper sector of the dendritic domain. This suggests a shift in the dendritic tree away from the region of primary input in layer IV toward the pial surface. We consider that the increases in dendritic parameters measured are a compensatory-type growth as we earlier suggested in the occipital cortex. The functional meaning of this growth remains undetermined.     

The rat amygdaloid nucleus: A morphometric right-left study

Our results indicate that Long-Evans male rats housed in standard conditions show no significant difference between the areas of sections of their left and right amygdalas. In contrast, the S₁ strain maze-bright animals have a significantly greater right amygdala than left. Furthermore, the data indicate an overall increase in mean $\text{(R + L)}\text{2}$ amygdala area from 6 to 400 days, except for a significant decrease in area from 26 to 90 days.     

Dendritic length in aged rats' occipital cortex: An environmentally induced response

The present investigation was the first to measure the lengths of dendrictic segments from aged animals in different environments to determine if the rates of retraction that occur with age can be influenced by the external environment. Our results show that the sixth-order segments, which represent the segments most distal to the cell body, are 86% longer in animals which have spent their final 30 days in an enriched environment compared with their littermates from standard laboratory conditions.     

Effect of age and enrichment on certain brain dimensions in Brattleboro rats deficient in vasopressin

As a sequel to our first report in the series of studies on the brains of Brattleboro rats, measurements in caudal diencephalon, subcortical telencephalon, hippocampus, and pyriform cortex were made in three groups each of male heterozygous and homozygous Brattleboro rats. One group raised in standard conditions was killed at 60 days of age, another raised in standard conditions was killed at 90 days of age, and a third group raised in standard conditions for 60 days was killed at 90 days of age after 30 days of enrichment. Comparing 60- and 90-day-old standard condition animals, the heterozygous rats showed a significant increase in height of the caudal diencephalon. Comparing 90-day-old enriched animals with the 90-day-old standard group, significant increases occurred in 8 of 12 comparisons. In comparing the two types of Brattleboro rats, heterozygous rats had significantly greater brain dimensions than homozygous rats in width of the diencephalon in the 60-day-old standard group, and in witth of the telencephalon in both the 90-day-old standard and enriched groups. Differences in brain measures between heterozygous and homozygous Brattleboro rats tended to increase with age. Enrichment appeared to prevent this age-related increase in the difference between brain dimensions in the two types of Brattleboro rat. The same pattern was reflected in body weight differences, and it may be due to a greater anabolic response to enrichment in homozygous rats than in heterozygous rats. We suggest that brain abnormalities associated with congenital absence of vasopressin increase with age, and may be ameliorated by repetitive arousal as occurs in enrichment.     

Environmental enrichment improves recent but not remote memory in association with a modified brain metabolic activation profile in adult mice

Environmental enrichment is known to improve learning and memory in adult rodents. Whereas the morphological changes underlying these beneficial effects are well documented, few studies have addressed the influence of this housing condition on the neuronal networks underlying memory processes. We assessed the effects of environmental enrichment on behavioural performances and brain metabolic activation during a memory task in mice. Adult mice were housed in standard (SC) or enriched (EC) conditions for 3 weeks. Then, recent and remote memory performances were measured in the passive avoidance test. After testing, brain metabolic activation was assessed through cytochrome oxidase (CO) activity. EC improved recent memory, in association with an increased metabolic activation in the frontal and prefrontal cortices and a decreased activation in the baso-lateral amygdala and the hippocampus. EC did not improve remote memory, and globally decreased CO activity. Our findings suggest the involvement of regions of pivotal importance during recent memory, such as the frontal cortex, in the beneficial effects of EC.     

Increased branching of basal dendrites on pyramidal neurons in the occipital cortex of homozygous Brattleboro rats in standard and enriched environmental conditions: A Golgi study

As a continuation of our previous reports in a series of studies on the brain of Brattleboro rats, the branching of basal dendrites of pyramidal neurons in the upper layers of the occipital cortex was quantified in three groups of male heterozygous and homozygous Brattleboro rats. One group raised in standard environmental conditions was killed at 60 days of age, and another from standard conditions was killed at 90 days of age. A third group from enriched environmental conditions was killed at 90 days of age after 30 days of enrichment. Comparing the two types of Brattleboro rats, the homozygous rats showed significantly more total dendritic branching segments per neuron in both the 60-day-old standard condition group and the 90-day-old enriched group. A similar measure (segments per primary branch) was also significantly greater in homozygous than in heterozygous rats at 60 days of age. In the 90-day-old enriched group, the homozygous rats showed a trend toward more segments per primary branch than the heterozygous rats. The results suggest that the complete absence of vasopressin produces metabolic effects which, at certain ages or in certain environmental conditions, increase the branching of basal dendrites of pyramidal neurons in the upper layers of the occipital cortex.     

Correlation between water intake and dendritic branching in homozygous Brattleboro rats: A Golgi study

This report is the fourth in a series on the brains of three groups of male Brattleboro rats. The present study concerns only homozygous Brattleboro rats. One group raised in standard environmental conditions was killed at 60 days of age, another raised in standard conditions was killed at 90 days of age, and a third group raised in standard conditions for 60 days was killed at 90 days of age after 30 days of environmental enrichment. Water intake (measured between 33 and 40 days of age) was compared with the number of branching segments on basal dendrites of pyramidal neurons in the upper layers of the parietal and occipital cortices. A significant negative correlation between water intake and the number of dendritic branching segments per primary branch was found in both parietal and occipital cortices in the 90-day-old standard condition group. In contrast, the 90-day-old enriched group showed a significant positive correlation between water intake and segments per primary branch in the parietal cortex, and a similar but nonsignificant response to enrichment in the occipital cortex. These results may reflect a cumulative effect of the congenital absence of vasopressin which is apparent by 90 days of age and which is modified by environmental enrichment. In the light of our previous data linking vasopressin and dendritic branching, we speculate that the neuropeptide, oxytocin, may be a physiologic correlate linking the behavioral parameter (water intake) and the anatomic parameter (dendritic branching) in homozygous Brattleboro rats.     

Increase in thickness of cerebral cortex in response to environmental enrichment in brattleboro rats deficient in vasopressin

Changes in cortical thickness were observed in male Brattleboro rats killed at 60 and 90 days of age from standard environmental conditions, and at 90 days of age after 30 days in an enriched condition. When 60- and 90-day-old standard animals were compared, both homozygous Brattleboro rats with diabetes insipidus and also heterozygous nondiabetic rats showed reduction in cortical thickness with age. When 90-day-old enriched animals were compared with the 90-day-old standard group: the homozygous rats with enrichment showed statistically significant thickening in frontal, parietal, and occipital cortices, and the heterozygous rats showed statistically significant thickening with enrichment in parietal and occipital regions. In both heterozygous and homozygous Brattleboro rats the most significant increases were in the occipital cortex. These results are in general agreement with previously reported developmental and enrichment studies in the normal Long-Evans strain of rats, with an important difference: both heterozygous and homozygous animals showed greater and more generalized response to enrichment. We speculate that this greater responsiveness to environmentally induced cortical thickening in the Brattleboro rats is due to increased arousal, and it may be related to alterations in norepinephrine concentration and/or turnover associated with absence of, or abnormalities in, vasopressin in the brain.     

Alterations in dendritic morphology of the prefrontal cortical and striatum neurons in the unilateral 6-OHDA-rat model of Parkinson's disease

We have studied the morphological changes of the dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and the medium spiny neurons of the caudate-putamen (CPu) and nucleus accumbens (NAcc) induced by the injection of 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). The unilateral 6-OHDA-induced lesion of the SNc was made in Wistar rats to produce the Parkinson model lesion. Two weeks after the injection, the testing of rotational behavior caused by amphetamine injection was done to assess the animals with lesions. Four weeks after the 6-OHDA injection, the morphology of the pyramidal cells of Layer 5 of the PFC and the medium spiny neurons of the CPu and NAcc were quantified by modified Golgi-Cox staining. The results showed that the length of dendrites, the branching, and the density of dendritic spines on the medium spiny neurons of the same side of the caudate-putamen lesion were significantly decreased in rats with the unilateral 6-OHDA-induced lesion of the SNc. The pyramidal neurons of the PFC and medium spiny neurons of the NAcc showed a decrease in the density of dendritic spines without significant changes in dendritic length or arborization. Our data suggest that the SNc lesion with the 6-OHDA, Hemiparkinsonism animal model may lead to altered neuronal plasticity in the CPu, NAcc, and PFC that may have participated in the emergence of the behavioral changes observed in these animals.     

Alterations in dendritic morphology of frontal cortical neurons after basal forebrain lesions in adult and aged rats

The nucleus basalis magnocellularis (NBM) is the major cholinergic projection to neocortex in the rat and plays a role in the modulation of cortical activity. Lesions of the NBM decrease thickness of lamina II–III of frontal cortex and decrease soma size of lamina II–III neurons. Additionally, aging produces changes in neuron size and numbers in the basal forebrain and frontal cortex of rats. We assessed dendritic changes in neurons from lamina II–III of frontal cortex in adult, middle-aged, and aged rats three months after unilateral lesions of the NBM. While lesions did not affect dendritic morphology in young adult rats, they decreased total dendritic length in middle-aged and aged rats, with dendritic alterations most pronounced in middle-aged rats. In middle-aged rats, lesion-induced changes in basilar arbor were apparently due to decreased dendritic branching: lesions markedly decreased the number of first-, second-, and third-order branches, but did not affect higher-order branching. In aged rats, lesions resulted in a small decrease in dendritic material proximal to the soma and a pronounced decrease in dendritic material distal to the soma, apparently due to a decrease in the length of terminal branches. These results suggest that the plasticity of neocortical neurons in the basalocortical system changes with age, and that early in aging this system may be particularly vulnerable to neural damage.     

Morphological and cellular changes within embryonic striatal grafts associated with enriched environment and involuntary exercise

Environmental enrichment (EE) and exercise have been implicated in influencing behaviour and altering neuronal processes associated with cellular morphology in both 'normal' and injured states of the CNS. Using a rodent model of Huntington's disease, we investigated whether prolonged EE or involuntary exercise can induce morphological and cellular changes within embryonic striatal transplants. Adult rats were trained on the Staircase test--requiring fine motor control to reach and collect reward pellets--prior to being lesioned unilaterally in the dorsal neostriatum with quinolinic acid. The lesioned animals received E15 whole ganglionic eminence cell suspension grafts followed by housing in EE or standard cages. Half of the animals in standard cages received daily forced exercise on a treadmill. The grafted animals showed significant functional recovery on both the Staircase test and in drug-induced rotation. Neither the housing conditions nor the training had an impact on the behaviour, with the exception of the treadmill reducing the ipsilateral drug-induced rotation observed amongst the lesioned animals. However, the animals housed in the EE had significantly increased striatal brain-derived neurotrophic factor (BDNF) levels, and graft neurons in these animals exhibited both greater spine densities and larger cell volumes. Animals on forced exercise regime had reduced BDNF levels and grafted cells with sparser spines. The study suggests that the context of the animal can affect the plasticity of transplanted cells. Appropriately exploiting the underlying, and yet unknown, mechanisms could lead the way to improved anatomical and potentially functional integration of the graft.     

Effect of the environment on the dendritic morphology of the rat auditory cortex

The present study aimed to identify morphological correlates of environment‐induced changes at excitatory synapses of the primary auditory cortex (A1). We used the Golgi‐Cox stain technique to compare pyramidal cells dendritic properties of Sprague‐Dawley rats exposed to different environmental manipulations. Sholl analysis, dendritic length measures, and spine density counts were used to monitor the effects of sensory deafness and an auditory version of environmental enrichment (EE). We found that deafness decreased apical dendritic length leaving basal dendritic length unchanged, whereas EE selectively increased basal dendritic length without changing apical dendritic length. On the contrary, deafness decreased while EE increased spine density in both basal and apical dendrites of A1 Layer 2/3 (LII/III) neurons. To determine whether stress contributed to the observed morphological changes in A1, we studied neural morphology in a restraint‐induced model that lacked behaviorally relevant acoustic cues. We found that stress selectively decreased apical dendritic length in the auditory but not in the visual primary cortex. Similar to the acoustic manipulation, stress‐induced changes in dendritic length possessed a layer‐specific pattern displaying LII/III neurons from stressed animals with normal apical dendrites but shorter basal dendrites, while infragranular neurons (Layers V and VI) displayed shorter apical dendrites but normal basal dendrites. The same treatment did not induce similar changes in the visual cortex, demonstrating that the auditory cortex is an exquisitely sensitive target of neocortical plasticity, and that prolonged exposure to different acoustic as well as emotional environmental manipulation may produce specific changes in dendritic shape and spine density. Synapse 64:97–110, 2010. © 2009 Wiley‐Liss, Inc.     

Alterations in medial prefrontal cortical activity and plasticity in rats with disruption of cortical development.

BACKGROUND: Psychiatric disorders such as schizophrenia are believed to emerge from an interaction of several factors. Thus, a genetic predisposition can lead to developmental compromises that may leave the system more susceptible to deficits induced by subsequent environmental variables such as stress. METHODS: The impact of neurodevelopmental interruption induced by exposure of rats prenatally to a compound methylazoxymethanol acetate (MAM) that disrupts neuronal proliferation was investigated using in vivo electrophysiologic recordings from the prefrontal cortex of adult rats. RESULTS: Prenatal exposure to MAM resulted in alterations in the medial prefrontal cortex indicative of a compromise in information processing. Specifically, we observed a disruption in activity patterns consistent with deficits in neuronal synchronization and abnormal augmentation of synaptic plasticity that was more severely disrupted by stress exposure than in normal animals. Furthermore, these deficits could be reversed by manipulating the mesocortical dopamine system. CONCLUSIONS: These results suggest that disruption of early cortical development causes impairments in medial prefrontal cortical function at adulthood that are more vulnerable to disruptive influences, despite the presence of only subtle structural alterations in the brain.     

Alterations in cortical and basal ganglia levels of opioid receptor binding in a rat model of l-DOPA-induced dyskinesia

Opioid receptor-binding autoradiography was used as a way to map sites of altered opioid transmission in a rat model of l-DOPA-induced dyskinesia. Rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathways sustained a 3-week treatment with l-DOPA (6 mg/kg/day, combined with 12 mg/kg/day benserazide), causing about half of them to develop dyskinetic-like movements on the side of the body contralateral to the lesion. Autoradiographic analysis of mu-, delta-, and kappa-opioid binding sites was carried out in the caudate-putamen (CPu), the globus pallidus (GP), the substantia nigra (SN), the primary motor area, and the premotor-cingulate cortex. The dopamine-denervating lesion alone caused an ipsilateral reduction in opioid radioligand binding in the CPu, GP, and SN, but not in the cerebral cortex. Chronic l-DOPA treatment affected opioid receptor binding in both the basal ganglia and the cerebral cortex, producing changes that were both structure- and receptor-type specific, and closely related to the motor response elicited by the treatment. In the basal ganglia, the most clear-cut differences between dyskinetic and nondyskinetic rats pertained to kappa opioid sites. On the lesioned side, both striatal and nigral levels of kappa binding densities were significantly lower in the dyskinetic group, showing a negative correlation with the rats' dyskinesia scores on one hand and with the striatal expression of opioid precursor mRNAs on the other hand. In the cerebral cortex, levels of mu and delta binding site densities were bilaterally elevated in the dyskinetic group, whereas kappa radioligand binding was specifically increased in the nondyskinetic cases and showed a negative correlation with the rats' dyskinesia scores. These data demonstrate that bilateral changes in cortical opioid transmission are closely associated with l-DOPA-induced dyskinesia in the rat. Moreover, the fact that dyskinetic and nondyskinetic animals often show opposite changes in opioid radioligand binding suggests that the motor response to l-DOPA is determined, at least in part, by compensatory adjustments of brain opioid receptors.