Adriana A. Alcantara

Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning.

This study compared the morphology of cerebellar cortex in adult female rats exposed for 1 month to repetitive exercise, motor learning, or an inactive condition. In the exercise conditions, rats that were run on a treadmill or housed with access to a running wheel had a shorter diffusion distance from blood vessels in the molecular layer of the paramedian lobule when compared to rats housed individually or rats that participated in a motor skill learning task. Rats taught complex motor skills substantially increased the volume of the molecular layer per Purkinje neuron and increased blood vessel number sufficiently to maintain the diffusion distance. These results dissociate angiogenesis associated with increased neuropil volume (as seen in the motor learning group) from angiogenesis associated with increased metabolic demands (as seen in the exercise groups). While the volume fraction of mitochondria did not differ among groups, the mitochondrial volume fraction per Purkinje cell was significantly increased in the motor skill rats. This appears to parallel the previously reported increase in synapses and associated neuropil volume change.

Dopamine D5 receptor localization on cholinergic neurons of the rat forebrain and diencephalon: A potential neuroanatomical substrate involved in mediating dopaminergic influences on acetylcholine release

The study of dopaminergic influences on acetylcholine release is especially useful for the understanding of a wide range of brain functions and neurological disorders, including schizophrenia, Parkinsons disease, Alzheimers disease, and drug addiction. These disorders are characterized by a neurochemical imbalance of a variety of neurotransmitter systems, including the dopamine and acetylcholine systems. Dopamine modulates acetylcholine levels in the brain by binding to dopamine receptors located directly on cholinergic cells. The dopamine D5 receptor, a D1‐class receptor subtype, potentiates acetylcholine release and has been investigated as a possible substrate underlying a variety of brain functions and clinical disorders. This receptor subtype, therefore, may prove to be a putative target for pharmacotherapeutic strategies and cognitive‐behavioral treatments aimed at treating a variety of neurological disorders. The present study investigated whether cholinergic cells in the dopamine targeted areas of the cerebral cortex, striatum, basal forebrain, and diencephalon express the dopamine D5 receptor. These receptors were localized on cholinergic neurons with dual labeling immunoperoxidase or immunofluorescence procedures using antibodies directed against choline acetyltransferase (ChAT) and the dopamine D5 receptor. Results from this study support previous findings indicating that striatal cholinergic interneurons express the dopamine D5 receptor. In addition, cholinergic neurons in other critical brain areas also show dopamine D5 receptor expression. Dopamine D5 receptors were localized on the somata, dendrites, and axons of cholinergic cells in each of the brain areas examined. These findings support the functional importance of the dopamine D5 receptor in the modulation of acetylcholine release throughout the brain. J. Comp. Neurol. 492:34–49, 2005.

Cocaine- and morphine-induced synaptic plasticity in the nucleus accumbens

The critical brain areas and molecular mechanisms involved in drug abuse and dependence have been extensively studied. Drug‐induced persistent behaviors such as sensitization, tolerance, or relapse, however, far outlast any previously reported mechanisms. A challenge in the field of addiction, therefore, has been to identify drug‐induced changes in brain circuitry that may subserve long‐lasting changes in behavior. This study examined behavioral changes and electron microscopic evidence of altered synaptic connectivity within the nucleus accumbens (NAc) following repeated administration of cocaine or morphine. The unbiased quantitative stereological physical disector method was used to estimate the number of synapses per neuron. Increases in the synapse‐to‐neuron ratio were found in the NAc shell of cocaine‐treated (49.1%) and morphine‐treated (55.1%) rats and in the NAc core of cocaine‐treated animals (49.1%). This study provides direct ultrastructural evidence of drug‐induced synaptic plasticity and identifies synaptic remodeling as a potential neural substrate underlying drug‐induced behavioral sensitization. Synapse, 2011.

The Roles of Experience in Different Developmental Information Stage Processes

There are at least 3 levels of experience involvement in the specification of connections in the nervous system; connections may be experience-independent, with no detectable influence of experience on their formation, experience-expectant, where synapses are generated in advance of the experience that selects a patterned subset of them for survival, and experience-dependent, the apparent form subserving adult learning and memory, where experience appears to trigger the formation of new connections. Molecular substrates of these three types of synapse formation are probably shared to a great extent, although, when synapses are triggered by experience, there must be regulators of any gene expression involved, structural proteins expressed that can bring about synapse formation, and, we argue, a local marker, that either initiates synaptogenesis or otherwise mediates the interval between nerve cell activity and the subsequent formation of a synapse. We discuss several candidates for these roles that we have studied.

Antibodies directed against microtubule proteins from Drosophila melanogaster cross react with similar proteins in the rat brain.

Monoclonal antibodies (Mabs) were used to delineate the localization of three proteins in rat cerebral cortex, hippocampus and cerebellum. The proteins were identified by Mabs directed against Drosophila melanogaster microtubule proteins (MTP). We have provisionally designated these proteins as Drosophila microtubule-associated proteins (DMAPs). The corresponding monoclonal antibodies are designated Mab DMAP-45, -55 and -66 indicating the molecular weights of each protein. All three Mabs cross-react with proteins of similar molecular weights in the rat brain. Correspondingly, these rat proteins are designated DMAPRs. DMAP-45 binds microtubules in an ATP-dependent manner. The molecular weight and subcellular localization of DMAP-45R differs significantly from previously described mammalian brain MAPs suggesting that it represents a novel MAP. Biochemical evidence suggests it may be an actin-related protein. DMAP-55R co-purifies stoichiometrically with rat brain microtubules and appears to be a previously undescribed isoform of tubulin. DMAP-66, which co-purifies stoichiometrically with Drosophila microtubules, does not do so in the rat brain. Immunohistochemistry performed with all three Mabs revealed a general pattern of staining of cell somata and dendrites in the cortex, hippocampus and cerebellum. Mab DMAP-55 also stained axons. In cerebral cortex all three Mabs preferentially, but not exclusively, stained layer V neuronal somata and dendrites. In hippocampus, Mabs DMAP-45 and -66 stained cell somata and dendrites in all hippocampal subfields, particularly the subiculum and CA3, whereas Mab DMAP-55 was most prevalent in mossy fibers. All three Mabs stain Purkinje cells in cerebellum with additional staining of cerebellar basket cells and Golgi cells observed with Mab DMAP-66.