Novel stimuli can be stressful for individuals with Autism Spectrum Disorders (ASD), though repeated exposure can reduce this effect. In Cntnap2-/- and Shank3B+/- mouse models of ASD, novel background odors impaired behavioral target odor recognition but that deficit improved with training. To investigate the neural basis of this improvement, we used widefield calcium imaging to measure olfactory bulb responses in Cntnap2-/- and Shank3B+/- mice and WT mice of either sex. Training with background odors enhanced both behavioral performance and neural discriminability of odor mixtures in both Cntnap2-/- and Shank3B+/- as well as WT mice. Naïve Cntnap2-/- and Shank3B+/- mice showed greater trial-to-trial neural variability than WT mice, but training stabilized neural responses. Critically, training produced a widespread reduction in olfactory bulb responses to background odors in ASD models, but not in WT mice. Thus, despite similar behavioral improvements as WT mice, Cntnap2-/- and Shank3B+/- mice relied on a...

Animal research, even when scrupulously regulated and performed with the upmost care and kindness, remains an ongoing ethical conundrum for many, including myself. I am a lover of animals, big and small.

We are at a unique time in history, when global large-scale projects are generating an unprecedented amount of data. Although much of this data is "open" and available—with analysis tools developed by a new generation of neuroinformaticians—some is still just beyond the reach of many neuroscientists. In this Short Course* from Neuroscience 2017, leaders in the neuroinformatics field highlight some of the most broadly accessible open datasets and help you embark on their independent scientific voyage of discovery. *This course includes demonstrations and tutorials using technical computing software (R-Studio, Python, Matlab).

Roberta Brinton, director of the University of Arizona Center for Innovation in Brain Science, and Bill Mobley, professor at the University of California San Diego School of Medicine, share an overview of translational research, including its key goals and challenges.

Humans rapidly update the control of an ongoing movement following changes in contextual parameters. This involves adjusting the controller to exploit redundancy in the movement goal, such as when reaching for a narrow or wide target, and adapting to dynamic changes such as velocity-dependent force fields (FFs). Although flexible control and motor adaptation are computationally distinct, the fact that both unfold within the same movement suggests that they interact functionally to support task-specific adjustments. To test this hypothesis, we conducted a series of experiments combining changes in the target structure and a force field presented separately or in combination. Seventy-six human participants (both sexes) took part in this study, with each experiment involving different participants. They were asked to reach for a target that could change from a narrow square to a wide rectangle between or during trials. Step loads were used to assess whether participants exploited target redundancy. In a separ...

Aberrant dopamine transmission is a hallmark of several psychiatric disorders. Dopamine neurons in the ventral tegmental area (VTA) display distinct activity states that are regulated by discrete afferent inputs. For example, burst firing requires excitatory input from the mesopontine-tegmentum, while dopamine neuron population activity, defined as the number of spontaneously active dopamine neurons, is thought to be dependent on inhibitory drive from the ventral pallidum (VP). Rodent models used to study psychiatric disorders, such as psychosis, consistently exhibit elevated dopamine neuron population activity, due to decreased tonic inhibition from the VP. However, it remains unclear whether the VP can modulate all dopamine neurons, or if only a specific subset of VTA dopamine neurons receive innervation from the VP to be recruited as required. This knowledge is critical for understanding dopamine regulation in normal and pathological conditions. Here, we used in vivo electrophysiology in male and female...

This study aims to examine the changes in AQP4 polarity and pericyte vascularity during temporal lobe epilepsy (TLE) progression, with the goal of identifying potential drug targets or strategies to delay the onset and progression of TLE. Chronic TLE was induced in male rats using pilocarpine. AQP4 polarity and pericyte vascular coverage were assessed by immunofluorescence. The effects of modulating AQP4 polarity on PTZ-induced TLE model using male mice were studied. Molecular mechanisms of AQP4 polarity were explored using Transwell co-culture and transcriptomics, validated at the protein level. ELISA was used to measure PDGF-BB levels in serum and cerebrospinal fluid. Following pilocarpine-induced chronic TLE model establishment, AQP4 polarity and pericyte vascular coverage rapidly increased but later declined, reaching the lowest levels in epileptic animals. Trifluoperazine prevented AQP4 redistribution, reduced seizure duration, and alleviated brain edema in PTZ-induced TLE mouse model. Transcriptomic ...

To conduct an effective graduate program assessment, you need to have clear ideas on what your teaching goals are and what you're trying to assess.

Alzheimer's disease (AD) has traditionally been associated with amyloid-β plaques, but growing evidence underscores the role of neuroinflammation in disease progression. The autoinflammatory hypothesis of AD suggests chronic immune dysfunction contributes to neuronal damage, making immune modulation a promising therapeutic strategy. Cannabidiol (CBD), a phytocannabinoid with anti-inflammatory properties, may offer therapeutic potential. This study investigates how CBD independently influences two key neuroinflammatory regulators in AD: the Indoleamine 2,3-dioxygenase (IDO) pathway and the cyclic GMP-AMP synthase (cGAS) pathway. Though mechanistically distinct, both shape CNS immune responses. Targeting these immune-metabolic axes provides a mechanistic alternative to amyloid- or tau-based approaches by addressing upstream drivers of neuroinflammation and immune dysregulation. Using the male 5XFAD transgenic AD mouse model, we administered CBD via inhalation and assessed IDO and cGAS expression using flow ...

Starting grad school brought me from the most poverty-stricken county in the country to Portland, Oregon. And yet, much of the advice I’ve received about surviving in grad school assumes I have the same background as other students. That I have the same fears and priorities they do. I started talking to my mentors about my background and the challenges I faced. From those discussions, my mentors came to understand my needs are different than other students’.