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Understanding brain function requires repeatable measurements of neural activity across multiple scales and multiple brain areas. In mice, large scale cortical neural activity evokes hemodynamic changes readily observable with intrinsic signal imaging (ISI). Pairing ISI with visual stimulation allows identification of primary visual cortex (V1) and higher visual areas (HVAs), typically through cranial windows that thin or remove the skull. These procedures can diminish long-term mechanical and physiological stability required for delicate electrophysiological measurements made weeks to months after imaging (e.g., in subjects undergoing behavioral training). Here, we optimized and directly validated an intact skull ISI system in mice. We first assessed how imaging quality and duration affect reliability of retinotopic maps in V1 and HVAs. We then verified ISI map retinotopy in V1 and HVAs with targeted, multi-site electrophysiology several weeks after imaging. Reliable ISI maps of V1 and multiple HVAs emerged with ~ 60 trials of imaging (65 ± 6 min), and these showed strong correlation to local field potential (LFP) retinotopy in superficial cortical layers (r2 = 0.74–0.82). This system is thus well-suited for targeted, multi-area electrophysiology weeks to months after imaging. We provide detailed instructions and code for other researchers to implement this system.

A fundamental task of the visual system is to respond to both increases and decreases of luminance with action potentials (ON and OFF responses(1–4)). OFF responses are stronger, faster, and more salient than ON responses in primary visual cortex (V1) of both cats(5,6) and primates(7,8), but in ferrets(9) and mice(10) ON responses can be stronger, weaker(11), or balanced(12) in comparison to OFF responses. These discrepancies could arise from differences in species, experimental techniques, or stimulus properties, particularly retinotopic location in the visual field, as has been speculated(9); however, the role of retinotopy for ON/OFF dominance has not been systematically tested across multiple scales of neural activity within species. Here, we measured OFF versus ON responses across large portions of visual space with silicon probe and whole-cell patch-clamp recordings in mouse V1 and lateral geniculate nucleus (LGN). We found that OFF responses dominated in the central visual field, whereas ON and OFF responses were more balanced in the periphery. These findings were consistent across local field potential (LFP), spikes, and subthreshold membrane potential in V1, and were aligned with spatial biases in ON and OFF responses in LGN. Our findings reveal that retinotopy may provide a common organizing principle for spatial modulation of OFF versus ON processing in mammalian visual systems.

A fundamental task of the visual system is to respond to luminance increments and decrements. In primary visual cortex (V1) of cats and primates, luminance decrements elicit stronger, faster, and more salient neural activity (OFF responses) than luminance increments (ON responses). However, studies of V1 in ferrets and mice show that ON responses may be stronger. These discrepancies may arise from differences in species, experimental conditions, or from measuring responses in single neurons versus populations. Here, we examined OFF versus ON responses across different regions of visual space in both single neurons and populations of mouse V1. We used high-density silicon probes and whole-cell patch-clamp recordings to assess OFF versus ON dominance in local field potential (LFP), single neuron, and membrane potential responses. Across these levels, we found that OFF responses clearly dominated in the central visual field, whereas ON responses were more evident in the periphery. These observations were clearest in LFP and subthreshold membrane potential. Our findings consolidate and resolve prior conflicting results and reveal that retinotopy may provide a common organizing principle for spatially biasing OFF versus ON processing in mammalian visual systems.

The mouse has become an influential model system for investigating the mammalian nervous system. Technologies in mice enable recording and manipulation of neural circuits during tasks where they respond to sensory stimuli by licking for liquid rewards. Precise monitoring of licking during these tasks provides an accessible metric of sensory-motor processing, particularly when combined with simultaneous neural recordings. There are several challenges in designing and implementing lick detectors during head-fixed neurophysiological experiments in mice. First, mice are small, and licking behaviors are easily perturbed or biased by large sensors. Second, neural recordings during licking are highly sensitive to electrical contact artifacts. Third, submillisecond lick detection latencies are required to generate control signals that manipulate neural activity at appropriate time scales. Here we designed, characterized, and implemented a contactless dual-port device that precisely measures directional licking in head-fixed mice performing visual behavior. We first determined the optimal characteristics of our detector through design iteration and then quantified device performance under ideal conditions. We then tested performance during head-fixed mouse behavior with simultaneous neural recordings in vivo. We finally demonstrate our device’s ability to detect directional licks and generate appropriate control signals in real time to rapidly suppress licking behavior via closed-loop inhibition of neural activity. Our dual-port detector is cost effective and easily replicable, and it should enable a wide variety of applications probing the neural circuit basis of sensory perception, motor action, and learning in normal and transgenic mouse models. NEW & NOTEWORTHY Mice readily learn tasks in which they respond to sensory cues by licking for liquid rewards; tasks that involve multiple licking responses allow study of neural circuits underlying decision making and sensory-motor integration. Here we design, characterize, and implement a novel dual-port lick detector that precisely measures directional licking in head-fixed mice performing visual behavior, enabling simultaneous neural recording and closed-loop manipulation of licking.

Youth gun violence is most often a group phenomenon yet most empirical examinations ignore this fact. Using interview data with 416 violent male offenders from two disadvantaged New York City neighborhoods, this paper examines the roles that the peer contexts play in explaining the nuanced patterns of respondent gun-related behaviors. We hypothesize that respondents who are comparatively more embedded in networks of peers who carry and use guns will also report greater involvement in serious gun violence. We found that guns were equated with self-protection and the most prevalent reason given for possession and carrying behaviors of peers. Belonging to a group of associates was also perceived to have protective value. Guns and armed peers played a role in heightened risk for lethal conflict. Peers are involved as co-offenders in the majority of gun events reported. We discuss the implications of our findings for violence intervention policy and future research.

PurposePrimary open angle glaucoma (POAG) is a leading cause of irreversible blindness in the elderly. Previous epidemiological studies have identified family history, ethnic origin, age, high intraocular pressure and diabetes mellitus as risk factors. However, it is difficult to assess the extent family history plays in this disease process. The Utah Population Database (UPDB), created by the University of Utah, has recently become a resource for which greater than 9 million records are available for use. The UPDB is divided into two major data sets from which family members can be identified, namely 1.6 million genealogy records and 2 million Utah birth certificates. This study utilizes these resources to assess the familial risk of POAG within the Utah Population.MethodsThe University of Utah’s hospital and clinic records were searched for patients with primary and chronic open angle glaucoma (ICD9 codes 365.04 and 365.11) between the years 1995 and 2005. A case-control analysis was then performed with specialized UPDB software that was modified to constrain the control and pedigree populations to over 1 million University of Utah-UPDB linked records. Controls were matched to cases by gender and birth year (±2.5years) with only one control being used per case. Population-attributable risk (PAR) to familial factors and relative risk (RR) were computed using conditional logistic regression (CLR).ResultsFrom the original 1.5 million medical records, 6198 patients with glaucoma were identified. Of these, 3391 met the inclusion criteria, which required patients to have at least one parent or one child in the UPDB. The PAR in this population was found to be 0.20, indicating 20% of the risk for glaucoma is attributable to genetic factors. CLR computations also showed a significantly increased relative risk (p

The Aerospace Corporation is sponsoring research into the development and use of Nanotechnology Instrumentation in support of Space Launch applications. The intent is to use nanotechnology-based commercial-off-the-shelf components (COTS) micro-electromechanical (MEMS) and in-house developed sensors as basis for a wired or wireless sensors instrumentation and detection system. As part of this effort, the Aerospace Materials and Mechanics Technology Center (MMTC) is supporting the development and testing of a wireless Multi-parameter Sensor (MPS) instrumentation system and a chemical microsensor for the detection of hydrogen chloride (HCl) gas in solid rocket motor exhaust plumes. This paper documents and describes the progress made in the development and testing of these MEMS-based instrumentation.