Biomedical subjects

D L Maier

Publications and source records attributed to D L Maier.

8 recordsLinked to original sources

PubMed1999

Disrupted cortical map and absence of cortical barrels in growth-associated protein (GAP)-43 knockout mice.

There is strong evidence that growth-associated protein (GAP-43), a protein found only in the nervous system, regulates the response of neurons to axonal guidance signals. However, its role in complex spatial patterning in cerebral cortex has not been explored. We show that mice lacking GAP-43 expression (-/-) fail to establish the ordered whisker representation (barrel array) normally found in layer IV of rodent primary somatosensory cortex. Thalamocortical afferents to -/- cortex form irregular patches in layer IV within a poorly defined cortical field, which varies between hemispheres, rather than the stereotypic, whisker-specific, segregated map seen in normal animals. Furthermore, many thalamocortical afferents project abnormally to widely separated cortical targets. Taken together, our findings indicate a loss of identifiable whisker territories in the GAP-43 -/- mouse cortex. Here, we present a disrupted somatotopic map phenotype in cortex, in clear contrast to the blurring of boundaries within an ordered whisker map in other barrelless mutants. Our results indicate that GAP-43 expression is critical for the normal establishment of ordered topography in barrel cortex.

Animals↗

PubMed1997

Calcium-binding protein phenotype defines metabolically distinct groups of neurons in barrel cortex of behaving hamsters.

Physiological/anatomical studies of rat frontal cortex in vitro have distinguished subpopulations of gamma-aminobutyric acid (GABA)-expressing inhibitory interneurons defined by expression of the calcium-binding proteins, parvalbumin (PV) and calbindin (CA). Using a novel 2DG/immunostaining technique to double-label hamster barrel cortex for metabolism and phenotype, we have recently shown that while many GABAergic neurons are heavily 2DG labeled during normal exploratory behavior, a subset of GABAergic cells shows relatively sparse 2DG labeling. For this study we used the 2DG/immunostaining technique to test whether, in awake behaving animals, calcium-binding protein expression in a given cell in barrel cortex (as indicated by immunohistochemistry for PV or CA) was related to the degree of 2DG labeling. We found that most PV+ cells were moderately to heavily 2DG labeled, while most CA+ cells were lightly 2DG labeled. Our data indicate that the PV+ and CA+ cells represent metabolically distinct subpopulations of GABAergic neurons in barrel cortex. This distinction corresponds well with the in vitro physiological and anatomical data from frontal cortex and suggests functional implications for the expression of PV and CA, or other colocalized factors, in normally functioning cortical circuitry.

Animals↗

PubMed1996

Widespread activation of barrel cortex by small numbers of neonatally spared whiskers.

Activity-dependent plasticity in rodent whisker barrel cortex was examined by means of high-resolution 2-deoxyglucose (2-DG) with immunohistochemical double labeling. Hamsters with all but one, two, or four follicles ablated on postnatal day 7 received 2-DG injections as adults. Autoradiograms of follicle-ablated animals showed heavy activation of the entire barrel field during normal behavior, despite the missing whiskers. The intensity of 2-DG labeling was significantly reduced if the whiskers spared after follicle ablation were trimmed prior to the 2-DG injection, demonstrating that the widespread activation was driven by the spared whiskers. This widespread metabolic activation of the adult barrel field after neonatal follicle ablation was in sharp contrast to the somatotopically appropriate 2-DG labeling in barrel fields of normal adults subject to acute trimming of most whiskers, but was similar to that seen in normal adult animals with all whiskers intact. The results demonstrate large-scale plasticity of barrel circuitry following neonatal sensory deprivation, and provide a powerful functional anatomical setting to investigate underlying mechanisms.

Afferent Pathways↗

PubMed1995

NMDA antagonism during development extends sparing of hindlimb function to older spinally transected rats.

Hindlimb weight support and bipedal stepping occur after spinal cord transection in neonatal rats (birth to 12 days of age) while the same lesion in 15-day and older animals results in permanent loss of these responses. Some compensatory change in lumbar spinal circuitry must occur after spinal transection in young animals subserving these hindlimb behaviors. In contrast, animals just a few days older are incapable of such compensatory responses. We have examined the hypothesis that neural activity leads to the postnatal loss of plasticity in spinal circuitry. We find that antagonism of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor with MK-801 in young animals extends the sparing of hindlimb function after spinal transection to older animals. This effect is not due to a non-specific depression of all exciatory drive to motor neurons since Ia to motor neurons synaptic transmission through non-NMDA receptors is preserved during MK-801 treatment. Acute administration of MK-801 at the time of spinal transection or chronic administration of MK-801 after postnatal day 17 has no effect on recovery of hindlimb function after spinal transection. These results highlight the importance of NMDA receptor activation in spinal circuit maturation.

Aging↗

PubMed1994

Behavioral and neuroanatomical consequences of a unilateral intraventricular infusion of AF64A and limitations on the neuroprotective effects of nimodipine.

The monoethylcholine aziridinium ion, AF64A, (3 nmol in 1 microliter) or artificial CSF (1 microliter) was infused unilaterally into the right dorsal lateral ventricle of male adult rats. Treatment with the L-type calcium channel antagonist, nimodipine (70 micrograms/kg b.wt.) or its vehicle was administered beginning before and for seven days following surgery. The infusion of AF64A reduced spontaneous alternation rates in the T-maze when compared to CSF and sham infused animals. AF64A-treated animals also took longer to reach the goal area in a complex maze task on specific trials relative to CSF and sham-infused animals. Locomotion and habituation to the open field did not differ between surgery groups. Unilateral AF64A significantly depleted acetylcholinesterase (AChE) positive terminals in the ipsilateral hippocampus and cell bodies in the ipsilateral medial septal area (MSA). Receptors for nerve growth factor (NGF-R), often colocalized with cholinergic cell bodies and terminals, also were depleted in the ipsilateral MSA of AF64A infused animals. Treatment with nimodipine did not have a neuroprotective effect on AF64A animals in either behavioral or histological results. However, some degree of protection was found in the vehicle-treated rats. This effect was likely a consequence of the stress of the injection procedure rather than the content of the vehicle, largely polyethylene glycol 400. Nimodipine-treated animals, regardless of surgery group, exhibited fewer emotional responses and had lower spontaneous alternation rates than untreated animals. The behavioral alterations found in the nimodipine groups are most easily explained in terms of altered emotionality. Overall our findings indicate that AF64A is a potent cholinotoxin that can selectively eliminate the ipsilateral septohippocampal cholinergic system when unilaterally infused into the lateral ventricle. It is possible that the mechanism of action of AF64A, like other nitrogen mustard analogues, involves disruption of basic processes involved in protein synthesis and DNA activities. Because of this, the toxic effects of the aziridinium mustard are independent of extracellular calcium and thus may not be susceptible to protection by calcium channel antagonists.

Acetylcholinesterase↗

PubMed1990

The residual spatial abilities of hippocampally lesioned rats can be enhanced by peripheral sympathetic-adrenal interventions.

In order to test the possible effectiveness of peripheral interventions with the adrenergic system for the alleviation of certain disorders that typically follow bilateral hippocampal lesions, rats with bilateral lesions of the hippocampus, the overlying neocortex, or sham operations were tested at two postoperative times in the Morris water maze, a frequently used "spatial task." Half of the animals in all groups were exposed to the adrenergic manipulations, i.e., a chronic, 7-day, systemic bretylium regime (5 mg/kg) and, in addition, a peripheral injection of norepinephrine (4 micrograms/kg) 30 min before the start of each training day. The other half received saline chronically and a single saline injection before each training day. Five days of training were given at each of the two training periods. The first began 7 days after surgery while the second began 33 days after surgery. As expected, the hippocampally lesioned animals were severely impaired in the task. The adrenergic treatment produced enhanced performances in the rats with hippocampal lesions at both training sessions, although the improvement was greatest at the later period. Although the animals receiving the pharmacologic treatment located the general area of the hidden platform better than the saline-treated animals with hippocampal lesions, the treated animals were still impaired, swimming directly to the hidden platform on fewer trials than did animals in the other groups.

Adrenal Glands↗

PubMed1989

Posttraining or pretest administration of nimodipine fails to affect retention of a simple learned association.

In previous experiments, the antagonist of voltage-sensitive calcium channels, nimodipine, given before training, enhanced the retention of an acquired preference for white-left relative to black-right in a two compartment apparatus. In the present experiments we attempted to determine if the retention effects produced by the drug could be attributed to effects occurring in the posttraining period. Various groups of rats received posttraining injections of nimodipine or its vehicle and two hours prior to testing received a second injection of nimodipine or its vehicle or no injection at all. All rats were tested for retention of the association twice, both 24 and 48 hr after acquisition. No posttraining or pretesting drug effects were found. This would support the view that the enhanced retention found after treatment with nimodipine found by ourselves and by others is due to a change in the animals at the time of acquisition.

Animals↗

PubMedDate not supplied

Use-dependent plasticity in barrel cortex: intrinsic signal imaging reveals functional expansion of spared whisker representation into adjacent deprived columns.

We used optical imaging of intrinsic cortical signals, elicited by whisker stimulation, to define areas of activation in primary sensory cortex of normal hamsters and hamsters subjected to neonatal follicle ablation at postnatal day seven (P7). Follicle ablations were unilateral, and spared either C-row whiskers or the second whisker arc. This study was done to determine if the intrinsic cortical connectivity pattern of the barrel cortex, established during the critical period, affects the process of representational plasticity that follows whisker follicle ablation. Additionally, we tested the ability to monitor such changes in individual cortical whisker representations using intrinsic signal imaging. Stimulation of a single whisker yielded peak activation of a barrel-sized patch in the somatotopically appropriate location in normal cortex. In both row and arc-spared animals, functional representations corresponding to spared follicles were significantly stronger and more oblong than normal. The pattern of activation differed in the row-sparing and arc-sparing groups, in that the expansion was preferentially into deprived, not spared areas. Single whisker stimulation in row-spared cases preferentially activated the corresponding barrel arc, while stimulation of one whisker in arc-spared cases produced elongated activation down the barrel row. Since whisker deflection normally has a net inhibitory effect on neighboring barrels, our data suggest that intracortical inhibition fails to develop normally in deprived cortical columns. Because thalamocortical projections are not affected by follicle ablation after P7, we suggest that the effects we observed are largely cortical, not thalamocortical.

Animals↗