PubMed Health⌕ Search

Biomedical subjects

Bryan Kolb

Publications and source records attributed to Bryan Kolb.

At least 37 records · Page 2Linked to original sources
PubMed2004

Evidence for bilateral control of skilled movements: ipsilateral skilled forelimb reaching deficits and functional recovery in rats follow motor cortex and lateral frontal cortex lesions.

Unilateral damage to cortical areas in the frontal cortex produces sensorimotor deficits on the side contralateral to the lesion. Although there are anecdotal reports of bilateral deficits after stroke in humans and in experimental animals, little is known of the effects of unilateral lesions on the same side of the body. The objective of the present study was to make a systematic examination of the motor skills of the ipsilateral forelimb after frontal cortex lesions to either the motor cortex by devascularization of the surface blood vessels (pial stroke), or to the lateral cortex by electrocoagulation of the distal branches of the middle cerebral artery (MCA stroke). Plastic processes in the intact hemisphere were documented using Golgi-Cox dendritic analysis and by intracortical microstimulation analysis. Although tests of reflexive responses in forelimb placing identified a contralateral motor impairment following both cortical lesions, quantitative and qualitative measures of skilled reaching identified a severe ipsilateral impairment from which recovery was substantial but incomplete. Golgi-impregnated pyramidal cells in the forelimb area showed an increase in dendritic length and branching. Electrophysiological mapping showed normal size forelimb representations in the lesioned rats relative to control animals. The finding of an enduring ipsilateral impairment in skilled movement is consistent with a large but more anecdotal literature in rats, nonhuman primates and humans, and suggests that plastic changes in the intact hemisphere are related to that hemisphere's contribution to skilled movement.

Animals↗
PubMed2004

Immediate constraint-induced movement therapy causes local hyperthermia that exacerbates cerebral cortical injury in rats.

Constraint-induced movement therapy (CIMT), which involves restraint of the nonimpaired arm coupled with physiotherapy for the impaired arm, lessens impairment and disability in stroke patients. Surprisingly, immediate ipsilateral forelimb immobilization exacerbates brain injury in rats. We tested whether immediate ipsilateral restraint for 7 days aggravates injury after a devascularization lesion in rats. Furthermore, we hypothesized that ipsilateral restraint aggravates injury by causing hyperthermia. In experiment 1, each rat received two lesions, one in the motor cortex and one in the visual cortex. Ipsilateral restraint increased only the motor cortex lesion. In additional rats, no differences in core temperature occurred after ipsilateral or contralateral restraint. Thus, ipsilateral restraint does not aggravate injury by a systemic side effect. In experiment 2, we hypothesized that ipsilateral restraint causes hyperthermia in the region surrounding the initial cortical lesion. Brain temperature, measured via telemetry, was significantly higher (approximately 1 degrees C for 24 h) with ipsilateral restraint. A third experiment similarly found that ipsilateral restraint aggravates injury and causes local cortical hyperthermia and that contralateral restraint with externally induced mild hyperthermia aggravates injury. In conclusion, immediate ipsilateral restraint aggravates injury apparently by localized events that include hyperthermia. Caution must be exercised in applying early CIMT to humans, as hyperthermia is detrimental.

Animals↗
PubMed2003

Recovery from infant medial frontal cortical lesions in rats is reversed by cortical lesions in adulthood.

Previous studies have shown that when the medial prefrontal cortex (mPFC) is removed at 7-10 days of age there is a spontaneous filling of the lesion cavity and a nearly complete restitution of behaviour. In the current study animals received mPFC lesions on postnatal day 10 and on day 160 the tissue occupying the mPFC region was again removed. Behavioural performance on the Morris water task was compared to animals with either only day 10 mPFC lesions or only day 160 mPFC lesions. Rats with the combined day 10 and day 160 lesions or day 160 lesions were severely impaired at the task whereas the rats with only day 10 lesions showed complete recovery. An analysis of dendritic arborization in pyramidal neurons adjacent to the lesion showed increased dendritic arborization in the basilar fields in both the P10 groups but this was not associated with functional recovery in the animals with the two mPFC lesions. It thus appears that the tissue that filled in the mPFC lesions on day 10 was functional.

Aging↗
PubMed2003

Do rats have a prefrontal cortex?

The lack of a single anatomical or functional definition of 'prefrontal cortex' has led to different and, in some respects, controversial views on the existence of a prefrontal cortex in non-primate mammals, in particular in rats. Until the classic paper by Rose and Woolsey [Res. Publ. Assoc. Nerv. Ment. Dis. 27 (1948) 210], the general idea was that a prefrontal cortex is unique to primate species. Rose and Woolsey's 'prefrontal cortex' definition was based upon a single anatomical criterion, i.e. the cortical projection area of the mediodorsal thalamic nucleus. Single criteria, however, do not appear to be sufficient for defining the prefrontal cortex. Therefore, other anatomical and functional characteristics are currently used to identify the prefrontal cortex in different species. Yet, recently the debate about the nature of the prefrontal cortex in non-primate species has been resumed. In the present paper we will compare the structural and functional characteristics of the prefrontal cortex of nonhuman primates and rats. We will argue that rats have a functionally divided prefrontal cortex that includes not only features of the medial and orbital areas in primates, but also some features of the primate dorsolateral prefrontal cortex.

Animals↗
PubMed2003

Recovery from early cortical damage in rats. IX. Differential behavioral and anatomical effects of temporal cortex lesions at different ages of neural maturation.

Rats were given lesions of the temporal association cortex on postnatal day 4 or 10, or in adulthood. Ninety days later they were trained on two visual tasks (visual-spatial navigation; horizontal-vertical stripes discrimination). Lesion animals were compared behaviorally and neuroanatomically to littermate sham control rats. The day 4 lesions produced a larger deficit in the navigation task than day 10 or adult lesions. There were no deficits in the discrimination task. Analysis of the brains showed that the day 4 lesions produced a smaller brain and thinner cortex than day 10 lesions. The day 10 lesions produced hypertrophy in the dendritic arborization of pyramidal cells in parietal cortex. The results are consistent with the general findings that perinatal cortical injury in rats produces more severe behavioral and morphological effects than similar lesions in the second week of life and that cortical lesions around day 10 lead to an increase in cortical synaptogenesis.

Aging↗
PubMed2003

Amphetamine or cocaine limits the ability of later experience to promote structural plasticity in the neocortex and nucleus accumbens.

Drugs of abuse and many other kinds of experiences share the ability to alter the morphology of neuronal dendrites and spines, the primary site of excitatory synapses in the brain. We hypothesized, therefore, that exposure to psychostimulant drugs might influence later experience-dependent structural plasticity. We tested this hypothesis by treating rats repeatedly with amphetamine or cocaine and then housing them in either a complex environment or standard laboratory cages for 3-3.5 mo. The brains were processed for Golgi-Cox staining, and the number of dendritic branches and the density of dendritic spines on medium spiny neurons in the nucleus accumbens and pyramidal cells in the parietal cortex were quantified. On most measures, prior treatment with amphetamine or cocaine interfered with the ability of experience in a complex environment to increase dendritic arborization and spine density. We conclude that in some brain regions, repeated exposure to psychomotor-stimulant drugs limits the ability of later experience to produce this form of synaptic plasticity, which may contribute to the persistent behavioral and cognitive deficits associated with drug abuse.

Amphetamine↗
PubMed2003

Environmental complexity has different effects on the structure of neurons in the prefrontal cortex versus the parietal cortex or nucleus accumbens.

Complex housing has been used widely as a model of experience-dependent change. Animals housed in complex environments typically show synaptogenesis throughout the sensory and motor cortex as well as the striatum and hippocampus, and thus it is generally assumed that such changes are likely to be found throughout the cerebrum. The purpose of the present study was to determine whether persistent alterations of dendritic morphology would be found in two regions that had previously not been examined, namely, the medial prefrontal region (Cg3) and nucleus accumbens (NAcc). The results show that housing female rats in complex environments for 3.5 months increased dendritic arborization on medium spiny neurons in the NAcc and on pyramidal cells in the somatosensory cortex (Par 1), but not in Cg3. Environmental complexity increased spine density in all three areas, however. The failure to find increased dendritic length or branching in Cg3 was unexpected. Thus, the data suggest that complex housing may not engage prefrontal neurons in the same manner as neurons in sensory or motor areas. It appears that complex housing may not produce generalized changes in cerebral morphology. The data further suggest that it is prudent to measure both dendritic length and spine density in studies of experience-dependent effects on synaptic plasticity.

Animals↗
PubMed2003

The location of persistent amphetamine-induced changes in the density of dendritic spines on medium spiny neurons in the nucleus accumbens and caudate-putamen.

Repeated intermittent treatment with amphetamine increases the density of dendritic spines on medium spiny neurons (MSNs) in the nucleus accumbens (NAcc). The purpose of this study was two-fold: (1) to determine whether amphetamine has similar effects on MSNs in the caudate-putamen (CPu) and (2) to determine if this effect is localized to distal dendrites, the site of convergence of dopamine (DA) and glutamate synapses in the striatum. An amphetamine treatment regimen that produced behavioral sensitization increased the density of dendritic spines on MSNs in both the NAcc and dorsolateral CPu. This effect was long lasting, because it was evident 3.5 months after the discontinuation of drug treatment. The increase in spine density was confined to distal dendrites of MSNs, and was not apparent on dendrites close to the cell body. It is concluded that amphetamine may preferentially reorganize synapses at the site of DA-glutamate interaction in the striatum, which may alter DA-glutamate signaling and thereby contribute to some of the persistent behavioral and psychological consequences of repeated exposure to psychostimulant drugs.

Amphetamine↗
PubMed2003

Role of the neocortex in the water maze task in the rat: a detailed behavioral and Golgi-Cox analysis.

The role of the neocortex in acquisition of the water maze task was investigated with both detailed behavioral and anatomical analyses. The neocortical areas examined were: (1). primary visual and posterior parietal areas Oc1 and Oc2M, (2). parietal area Par1, and (3). prefrontal areas Cg1, Cg3, IL, and part of Fr2 of Zilles, 1985. In Experiment 1, the effects of lesions in these areas were examined separately in different groups of naive male hooded rats. Additional rats were given water maze strategy pretraining before receiving a lesion. Strategy pretraining was used to separate water maze strategy learning from spatial learning to evaluate the contribution of the neocortical areas to these two components of task acquisition. All groups of naive lesioned rats were impaired in the task. In contrast, corresponding groups of pretrained lesioned rats performed as well as controls on all behavioral measures. In Experiment 2, the same neocortical areas lesioned in Experiment 1 were examined with the Golgi-Cox method to determine whether water maze training was associated with changes in the dendritic arborization of neocortical pyramidal cells. Contrary to expectations, no anatomical changes that could be ascribed to the behavioral training were seen in the areas and cortical layers examined. The data suggest that (1). these areas contribute to water maze strategy learning in naive rats, (2). none of the areas are crucially required for spatial learning provided rats are familiar with the general behavioral strategies required in the task before the lesion is made, and (3). any changes in neuronal morphology that occur as a consequence of the training may be subtle and widely distributed.

Animals↗
PubMed2003

Overview of cortical plasticity and recovery from brain injury.

The analysis of plastic changes in the nervous system is based on the assumption that the nervous system is not a static system but rather one that changes over time. Neural plasticity can be studied at many levels, beginning with behavior and then becoming progressively more microscopic by descending to the level of cerebral maps, synaptic organization, physiologic activities, molecular structure, and mitosis. This article considers each level in turn and then briefly describes how an understanding of the principles of plasticity can be used to initiate treatments for cerebral injury.

Cerebral Cortex↗
PubMed2003

Experience-dependent changes in dendritic arbor and spine density in neocortex vary qualitatively with age and sex.

Male and female Long-Evans hooded rats were placed in the complex environments for 3 months either at weaning (22 days), in young adulthood (120 days), or in senescence (24 months). The dendritic morphology of both the apical and basilar fields of layer III pyramidal cells was analyzed in both parietal and visual cortex. There were two novel results. First, although spine density was increased significantly with complex-housing in adulthood, it was decreased significantly by the same housing during development. Second, dendritic length was increased in both parietal and occipital cortex at all ages in males and was increased in adult females as well, but juvenile females showed no change in dendritic length in the occipital cortex and only a small effect on the apical field in parietal cortex. Thus, there are qualitative differences in the changes in spine density at different ages and the dendritic changes in response to complex versus isolated housing vary with sex, and in females, the changes vary with age as well. These results may explain some of the apparent inconsistencies in reports of spine and dendrite changes in the literature.

Age Factors↗
PubMed2003

Manipulation of gonadal hormones in neonatal rats alters the morphological response of cortical neurons to brain injury in adulthood.

The authors examined the effects of sex and neonatal hormones on the response of pyramidal cells (Layer III, parietal cortex) to injury of the medial frontal cortex in the adult rat. At birth, males were gonadectomized (GDX) or sham-operated. Females were given testosterone (T) or oil injections. In adulthood, rats that had been left intact at birth were GDX, and they then received bilateral medial frontal cortex lesions or sham surgery. Rats not exposed to T at birth exhibited losses of dendritic arbor (males GDX at birth) or dendritic spine density (oil-treated females). Compensation after cortical injury is dependent on the rat's sex and history of exposure to gonadal steroids.

Animals↗
PubMed2003

Odor tracking in rats with orbital frontal lesions.

Rats track self-, conspecific, and artificial odors to locate food. The orbital frontal cortex has been implicated in olfactory behavior, but whether it plays a role in a species-typical behavior, such as odor-guided navigation, has not been studied. Rats were trained to track 1 of 3 different odors deposited on a string. After rats were reliably tracking a scented string, they received a series of 2- and 3-odor discrimination tests. Next, all the rats received bilateral aspiration lesions of the orbital frontal cortex and experienced the same sequence of tasks. Rats learned to track and discriminate between different odors reliably. These results suggest that other areas of the brain mediate odor-guided navigation following damage to the orbital frontal cortex.

Animals↗
PubMed2003

Can a therapeutic dose of amphetamine during pre-adolescence modify the pattern of synaptic organization in the brain?

Stimulant drugs such as amphetamine have, for many decades, been the drugs of choice in the treatment of children with attention-deficit/hyperactivity disorder. However, little is known about their therapeutic mechanisms or about the consequences of their long-term exposure. In the present study we investigated whether repeated exposure of a low dose of amphetamine (0.5 mg/kg) to juvenile rats could induce long-term morphological alterations in the prefrontal cortex. In addition, to assess possible behavioural consequences of prolonged exposure to this drug, we examined whether changes in the motor response to various dopamine agonists occurred after this treatment. We found that this dose of amphetamine promotes plasma concentrations of amphetamine sulphate in juvenile rats to levels corresponding to the clinical range used for children with attention-deficit/hyperactivity disorder. Amphetamine (0.5 mg/kg; s.c.) was administered twice daily during postnatal days 22-34, and then the brains of the animals were evaluated 2 weeks later. This treatment produced an increase in dendritic length and branches of pyramidal neurons of the medial prefrontal cortex, but not in the nucleus accumbens. These changes were associated with an increase in the expression of calcium/calmodulin-dependent protein kinase II, a highly abundant signalling protein in the postsynaptic densities of excitatory synapses. Interestingly, amphetamine pre-treatment did not alter the motor response to various dopamine agonists, including amphetamine. These data suggest that clinical doses of stimulant drugs may be acting as a trophic support at the glutamatergic synapses, thereby enhancing dopamine-glutamate interactions in the prefrontal cortex.

Amphetamine↗
PubMed2002

Widespread but regionally specific effects of experimenter- versus self-administered morphine on dendritic spines in the nucleus accumbens, hippocampus, and neocortex of adult rats.

We studied the effects of self-administered (SA) vs. experimenter-administered (EA) morphine on dendritic spines in the hippocampal formation (CA1 and dentate), nucleus accumbens shell (NAcc-s), sensory cortex (Par1 and Oc1), medial frontal cortex (Cg3), and orbital frontal cortex (AID) of rats. Animals in the SA group self-administered morphine in 2-h sessions (0.5 mg/kg/infusion, i.v.) for an average of 22 sessions and animals in the EA group were given daily i.v. injections of doses that approximated the total session dose for matched rats in Group SA (average cumulative dose/session of 7.7 mg/kg). Control rats were given daily i.v. infusions of saline. One month after the last treatment the brains were processed for Golgi-Cox staining. In most brain regions (Cg3, Oc1, NAcc-s) morphine decreased the density of dendritic spines, regardless of mode of administration (although to a significantly greater extent in Group SA). However, only SA morphine decreased spine density in the hippocampal formation and only EA morphine decreased spine density in Par1. Interestingly, in the orbital frontal cortex morphine significantly increased spine density in both Groups SA and EA, although to a much greater extent in Group SA. We conclude: 1) Morphine has persistent (at least 1 month) effects on the density of dendritic spines in many brain regions, and on many different types of cells (medium spiny neurons, pyramidal cells, and granule cells); 2) The effect of morphine on spine density (and presumably synaptic organization) varies as a function of both brain region and mode of drug administration; and 3) The ability of morphine to remodel synaptic inputs in a regionally specific manner may account for the many different long-term sequelae associated with opioid use.

Animals↗
PubMed2002

Inosine induces axonal rewiring and improves behavioral outcome after stroke.

Cerebral infarct (stroke) often causes devastating and irreversible losses of function, in part because of the brain's limited capacity for anatomical reorganization. The purine nucleoside inosine has previously been shown to induce neurons to express a set of growth-associated proteins and to extend axons in culture and in vivo. We show here that in adult rats with unilateral cortical infarcts, inosine stimulated neurons on the undamaged side of the brain to extend new projections to denervated areas of the midbrain and spinal cord. This growth was paralleled by improved performance on several behavioral measures.

Animals↗
PubMed2002

Functional recovery and dendritic hypertrophy after posterior and complete cingulate lesions on postnatal day 10.

Rats received lesions of the posterior cingulate cortex or both the anterior and posterior cingulate cortex (total cingulate), or sham procedures, on postnatal Day 10. As adults, animals were trained in the Morris water task. Both the cingulate lesion groups showed substantial functional recovery relative to our previous studies of adult operates or animals with perinatal cingulate lesions. A Golgi analyis of layer III pyramidal cells in parietal cortex showed an increase in dendritic length in the lesion animals relative to sham controls, which is similar to previous findings for rats with anterior cingulate but not motor or parietal lesions. In addition, there was a partial regeneration of the anterior tissue in the total cingulates, which in some cases extended into the posterior region. This is consistent with earlier findings that anterior cingulate lesions around Day 10 stimulate neurogenesis. It appears that there is something special about the reparative processes and subsequent functional recovery that follow midline neocortical lesions.

Animals↗