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The dynamics of the ever-changing healthcare environment has influenced medical educators to take on the arduous task of modernising medical school curricula to incorporate the latest technologies and teaching modalities in an effort to bolster preparation of future clinicians. Howard University (HU) College of Medicine trains under-represented medical healthcare professionals to serve underserved, disenfranchised populations where physician shortage and limited access to healthcare disproportionately widen the wellness gap, thereby creating health disparities. To that end, the HU Health Sciences enterprise provides opportunities for implementing novel technology to promote excellence in teaching, superior clinical skills training and patient safety to produce the next generation of postgraduate physicians, clinical researchers and healthcare professionals. Here, pilot simulations employing a multifaceted case-based teaching approach integrating basic science lecture objectives with the acquisition of clinical skills germane to the assessment of cardiorespiratory function are revealed through a series of didactic lectures, educational videos, computer-assisted instruction modules and human patient simulation exercises. Recent establishment of the HU Clinical Skills and Simulation Center (Center) and its subsequent accreditation by the American College of Surgeons that classifies it as an Accredited Education Institute perpetuates and reaffirms the HU commitment to academic excellence. The Center’s mission is to provide an ideal learning environment to support educational curricula throughout the HU healthcare complex and to promote patient safety through …

In order to develop a model of persistent sensorimotor gating that did not require acute NMDA (N-methyl-D-aspartate) receptor blockade, adult female Sprague-Dawley rats were pre-treated with N-methyl-scopolamine (1 mg/kg s.c.), then administered MK-801 (dizocilpine, 5 mg/kg i.p.) along with two separate doses (5 mg/kg) of pilocarpine. The drug regimen was repeated four and eight days later. Controls received saline in lieu of any drug. Ten days after the last neurotoxic treatment, rats had a significant impairment (reduction) in pre-pulse inhibition (PPI). Each treatment group (neurotoxic treated and control) was then divided into two groups for treatment with saline or 0.5 mg/kg nicotine, administered s.c. twice daily from days 10 to 23. The rats were tested for sensorimotor gating on days 17 and 22 shortly after the morning nicotine administration. Nicotine did not affect the PPI in control animals. On day 17, PPI impairment was sustained in neurotoxically treated rats, regardless of saline or nicotine treatment. On day 22, however, the effect of neurotoxic treatment on PPI was totally absent in saline treated rats, whereas in nicotine treated rats, PPI impairment was still evident. Combination of nicotine and neurotoxic treatment also caused an up-regulation of high affinity nicotinic receptors in the cortex and the thalamus and apparent normalization of low affinity nicotinic receptors in the hippocampus. The findings indicate that muscarinic activation, in conjunction with neurotoxic NMDA receptor antagonism, produces relatively long-term impairment in auditory gating, a result relevant to modeling clinical observations of schizophrenia-associated symptoms. Contrary to expectation, nicotine administration in this model resulted in further impairment rather than amelioration of PPI. The results suggest a sustainable model of PPI impairment and possible role of nicotinic receptors in selective brain regions in this behavior.

Alzheimer's disease (AD) is the most common type of dementia afflicting the elderly. In addition to the presence of cortical senile plaques and neurofibrillary tangles, AD is characterized at autopsy by extensive degeneration of brainstem locus coeruleus (LC) neurons that provide noradrenergic innervation to cortical neuropil, together with relative stability of dopaminergic neuron number in substantia nigra (SN) and ventral tegmental area (VTA). The present study used design-based stereological methods to assess catecholaminergic neuronal loss in brains of double transgenic female mice that co-express two human mutations associated with familial AD, amyloid precursor protein (APP(swe)) and presenilin-1 (PS1(DeltaE9)). Mice were analyzed at two age groups, 3-6 months and 16-23 months, when deposition of AD-type beta-amyloid (Abeta) plaques occurs in cortical brain regions. Blocks of brain tissue containing the noradrenergic LC nucleus and two nuclei of dopaminergic neurons, the SN and VTA, were sectioned and sampled in a systematic-random manner and immunostained for tyrosine hydroxylase (TH), a specific marker for catecholaminergic neurons. Using the optical fractionator method we found a 24% reduction in the total number of TH-positive neurons in LC with no changes in SN-VTA of aged dtg APP/PS1 mice compared with non-transgenic controls. No significant differences were observed in numbers of TH-positive neurons in LC or SN-VTA in brains of young female dtg APP/PS1 mice compared to their age-matched controls. The findings of selective neurodegeneration of LC neurons in the brains of aged female dtg APP/PS1 mice mimic the neuropathology in the brains of AD patients at autopsy. These findings support the use of murine models of Abeta deposition to develop novel strategies for the therapeutic management of patients afflicted with AD.

Murine models that mimic the neuropathology of Alzheimer's disease (AD) have the potential to provide insight into the pathogenesis of the disease and lead to new strategies for the therapeutic management of afflicted patients. We used magnetic resonance imaging (MRI), design-based stereology, and high performance liquid chromatography (HPLC) to assess the age-related neuropathology in double transgenic mice that overexpress two AD-related proteins--amyloid precursor protein (APP) and presenilin 1 (PS1)--and age- and gender-matched wild-type (WT) controls. In mice ranging in age from 4-28 months, total volumes of the hippocampal formation (V (HF)) and whole brain (V (brain)) were quantified by the Cavalieri-point counting method on a systematic-random sample of coronal T2-weighted MRI images; the same stereological methods were used to quantify V (HF) and V (brain) after perfusion and histological processing. To assess changes in AD-type beta-amyloid (A beta) plaques, sections from the hippocampal formation and amylgdaloid complex of mice aged 5, 12, and 15 months were stained by Congo Red histochemistry. In aged mice with large numbers of amyloid plaques, systematic-random samples of sections were stained by GFAP immunocytochemistry to assess gender and genotype effects on total numbers of astrocytes. In addition, levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) and 5-HT metabolites were assayed by HPLC in fresh-frozen samples from neocortex, striatum, hippocampus, and brainstem. We confirmed age-related increases in amyloid plaques, beginning with a few plaques at 5 months of age and increasing densities by 12 and 15 months. At 15 months of age, there were robust genotype effects, but no gender effects, on GFAP-immunopositive astrocytes in the amygdaloid complex and hippocampus. There were no effects on monoamine levels in all brain regions examined, and no volume changes in hippocampal formation or whole brain as quantified on either neuroimages or tissue sections. Strong correlations were present between volume estimates from MRI images and histological sections, with about 85% reduction in mean V (HF) or mean V (brain) between MRI and processed histological sections. In summary, these findings show that the double transgenic expression of AD-type mutations is associated with age-related increases in amyloid plaques and astrocytosis; however, this model does not recapitulate the cortical atrophy or neurochemical changes that are characteristic of AD.

Synaptic function and neuronal organization in the auditory system has been shown to be reactive and malleable to experience. In this regard, deafness has important implications for auditory processing. Although the general blueprint for auditory circuits appears to be established before the onset of hearing, reduced auditory stimulation during postnatal development produces definable pathologic effects on the structural and functional features of synapses, cells, and pathways. Studying these congenital effects can be accomplished in a number of experimental models, but one of the most reliable is that of the deaf white cat. The deaf white cat is a known model of a cochleosaccular degeneration resembling the Scheibe deformity observed in humans. This chapter reviews our current understanding of auditory pathologies consequent to congenital deafness, highlighting observations made in the deaf white cat model. Most significantly, the restorative effects of electrical stimulation on the auditory system by way of cochlear implantation are presented. The available data demonstrate that synaptic organization in the auditory system is highly plastic to environmental influences.

The ability to hear, our perception of sound, is fundamental to how we perceive our external environment and interact with others using spoken language. Sound also plays a critical role in the normal development of the auditory system. In this review, we will discuss sound, hearing, and the role of hearing in brain development. We will examine the effect of deafness and the impact of cochlear implants on neuronal plasticity and auditory function.

The auditory experience is crucial for the normal development and maturation of brain structure and the maintenance of the auditory pathways. The specific aims of this review are (i) to provide a brief background of the synaptic morphology of the endbulb of Held in hearing and deaf animals; (ii) to argue the importance of this large synaptic ending in linking neural activity along ascending pathways to environmental acoustic events; (iii) to describe how the re-introduction of electrical activity changes this synapse; and (iv) to examine how changes at the endbulb synapse initiate trans-synaptic changes in ascending auditory projections to the superior olivary complex, the inferior complex, and the auditory cortex.

Congenital deafness results in synaptic abnormalities in auditory nerve endings. These abnormalities are most prominent in terminals called endbulbs of Held, which are large, axosomatic synaptic endings whose size and evolutionary conservation emphasize their importance. Transmission jitter, delay, or failures, which would corrupt the processing of timing information, are possible consequences of the perturbations at this synaptic junction. We sought to determine whether electrical stimulation of the congenitally deaf auditory system via cochlear implants would restore the endbulb synapses to their normal morphology. Three and 6-month-old congenitally deaf cats received unilateral cochlear implants and were stimulated for a period of 10–19 weeks by using human speech processors. Implanted cats exhibited acoustic startle responses and were trained to approach their food dish in response to a specific acoustic stimulus. Endbulb synapses were examined by using serial section electron microscopy from cohorts of cats with normal hearing, congenital deafness, or congenital deafness with a cochlear implant. Synapse restoration was evident in endbulb synapses on the stimulated side of cats implanted at 3 months of age but not at 6 months. In the young implanted cats, postsynaptic densities exhibited normal size, shape, and distribution, and synaptic vesicles had density values typical of hearing cats. Synapses of the contralateral auditory nerve in early implanted cats also exhibited synapses with more normal structural features. These results demonstrate that electrical stimulation with a cochlear implant can help preserve central auditory synapses through direct and indirect pathways in an age-dependent fashion. J. Comp. Neurol. 518:2382– 2404, 2010.

Acutely administered N-methyl-D-asparate (NMDA) antagonists are used to model schizophrenia, as measured by impairments in sensorimotor gating reflected in decreases in prepulse inhibition of the startle response (PPI). Aspects of acute NMDA receptor antagonism limit the applications of these models. The aim of this paper is to determine the long-term effects of developmental phencyclidine (PCP) treatment on sensorimotor gating in both male and female rats. Male and female Sprague Dawley rats were injected with PCP (10 mg/kg s.c.) on postnatal days (PN) 7, 9, and 11 and were tested for PPI on PN 32—34. The groups were then divided and some of the animals received a single dose of PCP (10 mg/kg s.c.) on PN 45. The animals were tested again for PPI at approximately 1, 4, and 6 weeks after the treatment. There were no significant effects of neonatal-only treatment. One week after the PN 45 treatment, animals that were treated as neonates and as adolescents (PCP/PCP) were significantly impaired in PPI in both sexes. Male and female PCP/PCP rats also had significant increases in acoustic startle response 4 weeks posttreatment, which subsequently declined. PPI impairments in both sexes recovered over time and the adolescent-only treated females showed significant increases (improvement) in PPI approximately 6 weeks posttreatment. These data suggest that treatment with an NMDA receptor antagonist during adolescence or early adulthood can produce a relatively long-term impairment of PPI (approximately 1 week) and that this effect is more pronounced in male animals.