Loss-of-function (LOF) Frazzled/DCC mutants disrupt synaptogenesis in the Giant Fiber (GF) System of Drosophila . We observed weaker physiology in LOF male and female specimens, characterized by longer latencies and reduced response frequencies between the GFs and the motor neurons. These physiological phenotypes are linked to a loss of gap junctions in the GFs, specifically the loss of the shaking-B(neural+16) isoform of innexin in the presynaptic terminal. We present evidence of Frazzled's role in gap junction regulation by utilizing the UAS-GAL4 system in Drosophila to rescue mutant phenotypes. Expression of various UAS-Frazzled constructs in a Frazzled LOF background was used to dissect the role of different parts of the Frazzled receptor in the assembly of electrical synapses. Expressing Frazzled’s intracellular domain in Frazzled LOF mutants rescued axon pathfinding and synaptogenesis. This is supported by the complementary result that Frazzled fails to rescue synaptic function when the transcription...

Reaching movements, while seemingly simple, involve complex motor control mechanisms that select specific trajectories from infinite possibilities. Despite inherent variability in volitional movements, both humans and monkeys frequently exhibit stereotyped trajectories. The literature has offered numerous explanations for invariant trajectory shapes, including a common planning space in hand space or joint space, as well as factors like kinetic energy (KE) minimization and sensory feedback. However, since most studies have relied on single-session data, crucial insights into the motor principles guiding trajectory selection and their evolution through extended practice remain underexplored. This study fills this gap by investigating how specific trajectories are selected and evolve with practice across multiple sessions, using data from two rhesus monkeys (one male, one female) performing a reaching task in a biomechanically constrained 2D setup. Our behavioral study challenges the idea of a common plannin...

Psychedelic drugs have garnered increasing attention for their therapeutic potential in treating a variety of psychiatric diseases, such as depression, anxiety, and substance use disorder. The claustrum (CLA), a brain area with remarkable interconnectivity to frontal cortices, has recently been shown to have a dense population of serotonin 2 receptors (5-HT2Rs) that are activated by psychedelics. Because psychedelic therapy can require as little as one treatment session, it has been speculated that psychedelics achieve their long-term remedial effects by inducing neuroplasticity in brain areas responsible for psychiatric disease states, such as the anterior cingulate cortex (ACC). However, the effects of psychedelics on synaptic plasticity in serotonin receptor-rich brain areas remain entirely unexplored. We applied presynaptic stimuli paired with postsynaptic action potentials (APs) to a subpopulation of CLA neurons projecting to ACC in male rats to find that the psychedelic drug, 2,5-dimethoxy-4-iodoamph...

Studying locomotor activity in animal models is crucial for understanding physiological, behavioral, and pathological processes. This study aimed to develop an artificial intelligence-based tracking system called Goblotrop, designed to localize rodents within their laboratory environment. The Goblotrop system uses two infrared cameras to record videos of rodents in their home cages. A neural network analyzes these videos to determine the rodent's position at each time point. By tracking changes in position over time, the system provides detailed insights into rodent behavior, including speed, mobility, and climbing activity. To evaluate the system's reliability, we utilized a starvation-induced hyperactivity model, employed as a female mouse model for anorexia nervosa. This model is characterized by pronounced hyperactivity, typically assessed using electronically monitored running wheels. Both the Goblotrop system and running wheel measurements demonstrated that starvation increases food-anticipatory acti...

The integration of olfactory and spatial information is critical for guiding animal behavior. The lateral entorhinal cortex (LEC) is reciprocally interconnected with cortical areas for olfaction and the hippocampus and thus ideally positioned to encode odor–place associations. Here, we used miniendoscopes to record neural activity in the mouse piriform cortex (PCx) and LEC. We show that in head-fixed mice, odor identity could be decoded from LEC ensembles but less accurately than from PCx. In male mice freely navigating a linear track, LEC ensemble activity at the odor ports was dominated by spatial information. Spatial position along the linear track could be decoded from LEC and PCx activity; however, PCx but not LEC exhibited strong behavior-driven modulation of positional information. Together, our data reveal that information about odor cues and spatial context is differentially encoded along the PCx–LEC axis.

The association between brain structural connectivity (BSC) and different subtypes of stroke has not been reported. The current study determined whether some BSC patterns may contribute to the risk of stroke. A two-sample, bidirectional, multivariate Mendelian randomization (MR) analysis was performed. Genome-wide association summary statistics for BSC were obtained from the GWAS Catalog at the European Bioinformatics Institute, while stroke outcome data were obtained from the FinnGen study for intracerebral hemorrhage (ICH) and from the MEGASTROKE Consortium for ischemic stroke (IS) and its subtypes. A colocalization analysis was performed to determine whether the association between BSC and stroke was driven by loci within genomic regions. Reverse MR was performed to evaluate potential stroke-induced changes in BSC. Among the significant findings, left hemisphere (LH) somatomotor network-to-LH salience/ventral attention network white matter (WM) structural connectivity (SC) [OR = 1.30; p  = 5.96 × 10−4; ...

A key process for successful working memory is to prioritize task-relevant information over distraction, i.e., to control attentional deployment. Here we investigate to what extent attentional control during a delayed match-to-sample task can be achieved when to-be-remembered items were presented unconsciously together with distracting information and with a prestimulus cue that indicated whether the target was likely to appear on the left or right side of the screen. This expectation was sometimes violated (20% of trials), requiring reorienting of attention to successfully solve the task. Moreover, the cue was uninformative of the exact location of the target, which could appear on the top, middle, or bottom part of the screen. Participants performed better than chance on unconscious trials only when the cue correctly indicated target side, suggesting an inability to reorient attention when the cues were invalid. Neural activity (fMRI BOLD signal change) in medial and lateral prefrontal cortex was signifi...

This webinar is exclusive for SfN members. Please log in for access. Join this interactive session as Khalid Elsaafien and Eric Krause discuss their paper, “Identification of Novel Cross-Talk between the Neuroendocrine and Autonomic Stress Axes Controlling Blood Pressure” with JNeurosci Editor-in-Chief Marina Picciotto. Attendees can submit questions at registration and live during the webinar. Below is the significance statement of Identification of Novel Cross-Talk between the Neuroendocrine and Autonomic Stress Axes Controlling Blood Pressure, published on May 26, 2021, in JNeurosci and authored by Khalid Elsaafien, Matthew K. Kirchner, Mazher Mohammed, Sophia A. Eikenberry, Chloe West, Karen A. Scott, Annette D. de Kloet, Javier E. Stern, and Eric G. Krause. The survival of an organism is dependent on meeting the energetic demands imposed by stressors. This critical function is accomplished by the CNS's ability to orchestrate simultaneous activities of neurosecretory and autonomic axes. Here, we unveil a novel signaling mechanism within the paraventricular nucleus of the hypothalamus that links excitation of neurons producing corticotropin-releasing-hormone with excitation of neurons controlling sympathetic nervous system activity and blood pressure. The implication is that chronic stress exposure may promote cardiometabolic disease by dysregulating the interneuronal cross-talk revealed by our experiments.

Careers in translational drug discovery offer exciting opportunities to apply your biomedical research training to the development of much-needed treatments for disease. While pursuing a career in drug discovery in the past has meant exiting the academic setting to join the pharmaceutical industry, this is no longer the case. Translational drug discovery efforts are occurring in a variety of settings including those in academia and the government. This Neuroscience 2017 event provides an overview of career opportunities in the pharmaceutical industry, academic drug discovery centers, and NIH Intramural Research Programs and showcases examples of how basic and innovative biology can be turned into a drug discovery program in a variety of research settings that will lead to new medicines for patients who need them.

Sensory attenuation of auditory evoked potentials (AEPs), particularly N1 and P2 components, has been widely demonstrated in response to simple, repetitive stimuli sequences of isolated synthetic sounds. It remains unclear, however, whether these effects generalize to complex soundscapes where temporal and acoustic features vary more broadly and dynamically. In this study, we investigated whether the inter-onset interval (IOI), the time between successive sound events, modulates AEP amplitudes in a complex auditory scene. We derived acoustic onsets from a naturalistic soundscape and applied temporal response function (TRF) analysis to EEG data recorded from normal hearing human listeners (N = 22, 16 females, 6 males). Our results showed that shorter IOIs are associated with attenuated N1 and P2 amplitudes, replicating classical adaptation effects in a naturalistic sound scape. These effects remained stable when controlling for other acoustic features such as intensity and envelope sharpness and across diff...