Robbin Gibb

A method for vibratome sectioning of Golgi-Cox stained whole rat brain.

A method for impregnating the whole rat brain with Golgi-Cox stain and sectioning with the vibratome is described. The method is simple, inexpensive and provides good resolution of dendrites and spines.

Age, experience and the changing brain.

In this review, various aspects of how environmental experience effects the structure of the cortex at different times in the age of the animal are summarized. The interactions of brain injury and sex on the age-dependent plastic changes in the cortex are also considered. Finally, we have attempted to reach some general conclusions that describe the effects of age, experience, sex, and injury on the cortex.

Experience and the developing prefrontal cortex

The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time. It has a prolonged development, which allows the acquisition of complex cognitive abilities through experience but makes it susceptible to factors that can lead to abnormal functioning, which is often manifested in neuropsychiatric disorders. When the PFC is exposed to different environmental events during development, such as sensory stimuli, stress, drugs, hormones, and social experiences (including both parental and peer interactions), the developing PFC may develop in different ways. The goal of the current review is to illustrate how the circuitry of the developing PFC can be sculpted by a wide range of pre- and postnatal factors. We begin with an overview of prefrontal functioning and development, and we conclude with a consideration of how early experiences influence prefrontal development and behavior.

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.

Embryonic and Postnatal Injections of Bromodeoxyuridine Produce Age-Dependent Morphological and Behavioral Abnormalities

The mitotic marker 5-bromodeoxyuridine (BrdU) was injected twice daily (60 mg/kg) into pregnant hooded rats on one of embryonic days (E) 11, 12, 13, 15, 17, or 21, or into rat pups on postnatal day (P) 10. The principal findings were the following: (1) BrdU exposure on E11 produces profound effects on body morphology, and animals must be fed a special diet because of chronic tooth abnormalities; (2) BrdU exposure at E17 or earlier produces a change in coat spotting pattern, the precise pattern varying with age; (3) BrdU exposure on E15 or earlier produces a reduction in both brain and body weight; (4) BrdU exposure on E17 or earlier reduces cortical thickness; (5) BrdU exposure on E11–E13 and at P10 reduces cerebellar size relative to cerebral size; (6) spatial learning is significantly affected after injections of BrdU at E11–E17, but the largest effect is on E17; (7) the deficit in spatial learning may be related in part to a reduction in visual acuity; and (8) skilled forelimb ability is most disrupted after BrdU exposure at E15 but is also impaired after injections on E13 or earlier. BrdU thus has teratological effects on body, brain, and behavior that vary with the developmental age of the fetus or infant.

Cortical Plasticity and the Development of Behavior After Early Frontal Cortical Injury

It has been known for over 100 years that frontal lobe injury in children is often associated with considerably more functional recovery than after similar injury in adulthood. Systematic study of frontal cortical injury in laboratory animals has shown that this recovery is tightly tied to developmental age: There is a brief window of time during cortical development during which the brain is able to compensate. Simply being young is not sufficient because injury prior to this critical period leads to miserable behavioral outcomes. For humans, the least favorable time for cortical injury is likely at the end of the gestational period, perhaps including the 1st month or so of life whereas the most favorable time is around 1 to 2 years of age. In addition to age, the extent of behavioral recovery is influenced by age at assessment, the nature of the behavioral assessment, sex, and lesion size. Anatomical studies have shown that functional recovery following early cortical injury is correlated with a reorganization of remaining cortical circuitry, including increased dendritic arborization and increased spine density. Recovery, and the compensatory anatomical changes, can also be potentiated by application of different treatments including behavioral therapy, trophic factors, and neuromodulators. Finally, there is preliminary evidence in laboratory animals to suggest that it may be possible to induce neural regeneration in the injured brain and that the regenerated brain functions to support functional recovery.

Prenatal Stress Alters Dendritic Morphology and Synaptic Connectivity in the Prefrontal Cortex and Hippocampus of Developing Offspring

The current study used stereological techniques in combination with Golg‐Cox methods to examine the neuroanatomical alterations in the prefrontal cortex and hippocampus of developing offspring exposed to gestational stress. Morphological changes in dendritic branching, length, and spine density, were examined at weaning along with changes in actual numbers of neurons. Using this information we generated a gross estimation of synaptic connectivity. The results showed region‐specific and sex‐dependent alterations to neuroanatomy in response to prenatal stress. The two regions of the prefrontal cortex, medial prefrontal, and orbital prefrontal cortices, exhibited sexually dimorphic, opposite changes, in synaptic connectivity in response to the same experience. Both male and female offspring demonstrated a loss of neuron number and estimated synapse number in the hippocampus despite exhibiting increased spine density. The results from this study suggest that prenatal stress alters normal development and the organization of neuronal circuits in both neocortex and hippocampus early in development and thus likely influences the course of later experience‐dependent synaptic changes. Synapse, 2012.

Intensity matters: brain, behaviour and the epigenome of prenatally stressed rats

There is a general consensus that prenatal stress alters offspring brain development, however, the details are often inconsistent. Hypothesizing that variation to the level of stress would produce different maternal experiences; this study was designed to examine offspring outcomes following a single prenatal stress paradigm at two different intensities. Pregnant Long Evans rats received mild, high, or no-stress from gestational days 12-16. Offspring underwent early behavioural testing and global methylation patterns were analysed from brain tissue of the frontal cortex and hippocampus. The two different prenatal stress intensities produced significantly different and often, opposite effects in the developing brain. Mild prenatal stress decreased brain weight in both males and females, whereas extreme stress increased female brain weight. Mild prenatal stress slowed development of sensorimotor abilities and decreased locomotion, whereas high prenatal stress also slowed development of sensorimotor learning but increased locomotion. Finally, mild prenatal stress increased global DNA methylation levels in the frontal cortex and hippocampus whereas high prenatal stress was associated with a dramatic decrease. The data from this study provide evidence to support a dose-dependent effect of prenatal stress on multiple aspects of brain development, potentially contributing to long-term outcomes.

Possible anatomical basis of recovery of function after neonatal frontal lesions in rats

Rats given medial frontal lesions on Postnatal Day 1 or Day 10 were trained on the Morris water task on Days 19-21 or Days 56-58. The operated groups were equally impaired at the water task on Days 19-21, but the Day 10 rats had recovered by 56 days. Dendritic arborization and spine density were analyzed in parietal layer II-III pyramidal cells. At Day 60, but not at Day 22, the Day 10 animals had more dendritic spines per unit dendritic length than did the controls or Day 1 rats. Thus, there was functional recovery rather than sparing after frontal lesions at 10 days, and the recovery was correlated with an increase in dendritic spines.

Neural compensations after lesion of the cerebral cortex.

Functional improvement after cortical injury can be stimulated by various factors including experience, psychomotor stimulants, gonadal hormones, and neurotrophic factors. The, timing of the administration of these factors may be critical, however. For example, factors such as gonadal hormones, nerve growth factor, or psychomotor stimulants may act to either enhance or retard recovery, depending upon the timing of administration. Nicotine, for instance, stimulates recovery if given after an injury but is without neuroprotective effect and may actually retard recovery if it is given only preinjury. A related timing problem concerns the interaction of different treatments. For example, behavioral therapies may act, in part, via their action in stimulating the endogenous production of trophic factors. Thus, combining behavioral therapies with pharmacological administration of compounds to increase the availability of trophic factors enhances functional outcome. Finally, anatomical evidence suggests that the mechanism of action of many treatments is through changes in dendritic arborization, which presumably reflects changes in synaptic organization. Factors that enhance dendritic change stimulate functional compensation, whereas factors that retard or block dendritic change block or retard compensation.