Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND).

Early in the HIV epidemic, the central nervous system (CNS) was recognized as a target of infection and injury in the advanced stages of disease. Though the most severe forms of HIV-associated neurocognitive disorder (HAND) related to severe immunosuppression are rare in the current era of widespread combination antiretroviral therapy (cART), evidence now supports pathological involvement of the CNS throughout the course of infection. Recent work suggests that the stage for HIV neuropathogenesis may be set with initial viral entry into the CNS, followed by initiation of pathogenetic processes including neuroinflammation and neurotoxicity, and establishment of local, compartmentalized HIV replication that may reflect a tissue reservoir for HIV. Key questions still exist as to when HIV establishes local infection in the CNS, which CNS cells are the primary targets of HIV, and what mechanistic processes underlie the injury to neurons that produce clinical symptoms of HAND. Advances in these areas will provide opportunities for improved treatment of patients with established HAND, prevention of neurological disease in those with early stage infection, and understanding of HIV tissue reservoirs that will aid efforts at HIV eradication.

Normalization in mouse primary visual cortex.

When multiple stimuli appear together in the receptive field of a visual cortical neuron, the response is typically close to the average of that neuron's response to each individual stimulus. The departure from a linear sum of each individual response is referred to as normalization. In mammals, normalization has been best characterized in the visual cortex of macaques and cats. Here we study visually evoked normalization in the visual cortex of awake mice using optical imaging of calcium indicators in large populations of layer 2/3 (L2/3) V1 excitatory neurons and electrophysiological recordings across layers in V1. Regardless of recording method, mouse visual cortical neurons exhibit normalization to varying degrees. The distributions of normalization strength are similar to those described in cats and macaques, albeit slightly weaker on average.

Normalization in mouse primary visual cortex.

When multiple stimuli appear together in the receptive field of a visual cortical neuron, the response is typically close to the average of that neuron's response to each individual stimulus. The departure from a linear sum of each individual response is referred to as normalization. In mammals, normalization has been best characterized in the visual cortex of macaques and cats. Here we study visually evoked normalization in the visual cortex of awake mice using imaging of calcium indicators in large populations of layer 2/3 (L2/3) V1 excitatory neurons and electrophysiological recordings across layers in V1. Regardless of recording method, mouse visual cortical neurons exhibit normalization to varying degrees. The distributions of normalization strength are similar to those described in cats and macaques, albeit slightly weaker on average.

Supporting Inclusive Learning Environments and Professional Development in Medical Education Through an Identity and Inclusion Initiative.

In 2015, the Pritzker School of Medicine experienced increasing student interest in the changing sociopolitical landscape of the United States and the interaction of these events with student and patient identity. To address this interest, an Identity and Inclusion Steering Committee was formed and formally charged with "providing ongoing direction for programs and/or curricula at Pritzker that support an inclusive learning environment and promote respectful and effective communication with diverse patients and colleagues around issues of identity." The authors describe this committee's structure and steps taken by the committee to create an inclusive community of students at Pritzker characterized by learning through civil discourse. Initiatives were guided by a strategy of continuous quality improvement consisting of regular iterative evaluation, ongoing school-wide engagement, and responsiveness to issues and concerns as they emerged. Data collected over the committee's 4-year existence demonstrate significant improvement in students' sense of inclusion and respect for different perspectives on issues related to identity, such as access to health care, racialized medicine, safe spaces, and nursing labor strikes. The authors discuss several principles that support the development of an inclusive community of students as well as challenges to the implementation of such programming. They conclude that a strategy of continuous quality improvement guided by values of social justice, tolerance, and civil discourse can build community inclusion and enhance medical training for the care of diverse patient populations.

Decreased subcortical cholinergic arousal in focal seizures.

Impaired consciousness in temporal lobe seizures has a major negative impact on quality of life. The prevailing view holds that this disorder impairs consciousness by seizure spread to the bilateral temporal lobes. We propose instead that seizures invade subcortical regions and depress arousal, causing impairment through decreases rather than through increases in activity. Using functional magnetic resonance imaging in a rodent model, we found increased activity in regions known to depress cortical function, including lateral septum and anterior hypothalamus. Importantly, we found suppression of intralaminar thalamic and brainstem arousal systems and suppression of the cortex. At a cellular level, we found reduced firing of identified cholinergic neurons in the brainstem pedunculopontine tegmental nucleus and basal forebrain. Finally, we used enzyme-based amperometry to demonstrate reduced cholinergic neurotransmission in both cortex and thalamus. Decreased subcortical arousal is a critical mechanism for loss of consciousness in focal temporal lobe seizures.