Neocortical Interneurons: From Diversity, Strength

Interneurons in the neocortex of the brain are small, locally projecting inhibitory GABAergic cells with a broad array of anatomical and physiological properties. The diversity of interneurons is believed to be crucial for regulating myriad operations in the neocortex. Here, we describe current theories about how interneuron diversity may support distinct neocortical processes that underlie perception

Arousal and Locomotion Make Distinct Contributions to Cortical Activity Patterns and Visual Encoding

SummarySpontaneous and sensory-evoked cortical activity is highly state-dependent, yet relatively little is known about transitions between distinct waking states. Patterns of activity in mouse V1 differ dramatically between quiescence and locomotion, but this difference could be explained by either motor feedback or a change in arousal levels. We recorded single cells and local field potentials from area V1 in mice head-fixed on a running wheel and monitored pupil diameter to assay arousal. Using naturally occurring and induced state transitions, we dissociated arousal and locomotion effects in V1. Arousal suppressed spontaneous firing and strongly altered the temporal patterning of population activity. Moreover, heightened arousal increased the signal-to-noise ratio of visual responses and reduced noise correlations. In contrast, increased firing in anticipation of and during movement was attributable to locomotion effects. Our findings suggest complementary roles of arousal and locomotion in promoting functional flexibility in cortical circuits.Video Abstrac

Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits.

Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach involves a microscope with an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism. We also introduce a viral transduction method for robust and widespread gene delivery in the mouse brain. These approaches allow us to identify the behavioral state-dependent functional connectivity of pyramidal neurons and vasoactive intestinal peptide-expressing interneurons with long-range cortical networks. Our imaging system provides a powerful strategy for investigating cortical architecture across a wide range of spatial scales

Therapeutic Use of Self and Fieldwork Experience: An Exploration of the Art and Science of Occupational Therapy

The clinical practice of occupational therapy has been described as a blend of both art and science. For occupational therapy students, Level II fieldwork experiences offer early opportunities to refine both client-centered attitudes and scientific aptitude in relationship-based caregiving. In this retrospective study, researchers examined the ability to predict final Fieldwork Performance Evaluation scores from the following non-cognitive (i.e., art) and cognitive (i.e., science) variables: ranked student responses to the Self-Assessment of Modes Questionnaire (v.II); undergraduate grade point average (GPA; cumulative and science), and Graduate Record Examination (GRE) scores (quantitative, verbal, and analytic). Using a series of simple linear regressions, researchers analyzed data from sixty-nine master’s-level occupational therapy students. For the first Level II fieldwork experience, empathizing and empathizing-revised modes appeared to be a significant predictor with moderate, positive correlation coefficients (p=.008, r=.329; p=.01, r=.296, respectively). For the second Level II fieldwork experience, collaborating and instructing modes appeared to be significant predictors (p=.036, r= -.255; p=.037, r=.254 respectively). GPA and GRE scores were not predictive of fieldwork success. The degree to which art and science shape expectations for relationship-based client interactions during fieldwork experiences requires further investigation. However, calling attention to occupational therapy students’ preferred communication modes highlight how client interactions may be shaped to fit the students’ natural tendencies rather than the needs of the client

Targeted optogenetic stimulation and recording of neurons in vivo using cell-type-specific expression of Channelrhodopsin-2

A major long-term goal of systems neuroscience is to identify the different roles of neural subtypes in brain circuit function. The ability to causally manipulate selective cell types is critical to meeting this goal. This protocol describes techniques for optically stimulating specific populations of excitatory neurons and inhibitory interneurons in vivo in combination with electrophysiology. Cell type selectivity is obtained using Cre-dependent expression of the light-activated channel Channelrhodopsin-2. We also describe approaches for minimizing optical interference with simultaneous extracellular and intracellular recording. These optogenetic techniques provide a spatially and temporally precise means of studying neural activity in the intact brain and allow a detailed examination of the effect of evoked activity on the surrounding local neural network. Injection of viral vectors requires 30–45 min, and in vivo electrophysiology with optogenetic stimulation requires 1–4 h.National Institutes of Health (U.S.)National Science Foundation (U.S.)Simons FoundationNational Institutes of Health (U.S.). Pioneer AwardNational Eye Institue (K99 Award)Knut and Alice Wallenberg Foundation (Postdoctoral Fellowship)Brain & Behavior Research Foundation. Young Investigator AwardThomas F. Peterse

Driving fast-spiking cells induces gamma rhythm and controls sensory responses,”

Cortical gamma oscillations (20280 Hz) predict increases in focused attention, and failure in gamma regulation is a hallmark of neurological and psychiatric disease. Current theory predicts that gamma oscillations are generated by synchronous activity of fast-spiking inhibitory interneurons, with the resulting rhythmic inhibition producing neural ensemble synchrony by generating a narrow window for effective excitation. We causally tested these hypotheses in barrel cortex in vivo by targeting optogenetic manipulation selectively to fast-spiking interneurons. Here we show that light-driven activation of fast-spiking interneurons at varied frequencies (82200 Hz) selectively amplifies gamma oscillations. In contrast, pyramidal neuron activation amplifies only lower frequency oscillations, a cell-type-specific double dissociation. We found that the timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses. Our data directly support the fast-spiking-gamma hypothesis and provide the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation. Brain states characterized by rhythmic electrophysiological activity have been studied intensively for more than 80 years Cell-type-specific expression of channelrhodopsin-2 To test directly the hypothesis that FS interneuron activity in an in vivo cortical circuit is sufficient to induce gamma oscillations, we used the light-sensitive bacteriorhodopsin Chlamydomonas reinhardtii channelrhodopsin-2 (ChR2), a cation channel activated by ,470 nm blue ligh

Noninvasive optical inhibition with a red-shifted microbial rhodopsin

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light–induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.McGovern Institute for Brain Research at MIT (Razin Fellowship)United States. Defense Advanced Research Projects Agency. Living Foundries Program (HR0011-12-C-0068)Harvard-MIT Joint Research Grants Program in Basic NeuroscienceHuman Frontier Science Program (Strasbourg, France)Institution of Engineering and Technology (A. F. Harvey Prize)McGovern Institute for Brain Research at MIT. Neurotechnology (MINT) ProgramNew York Stem Cell Foundation (Robertson Investigator Award)National Institutes of Health (U.S.) (New Innovator Award 1DP2OD002002)National Institute of General Medical Sciences (U.S.) (EUREKA Award 1R01NS075421)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1RC1MH088182)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (Career Award CBET 1053233)National Science Foundation (U.S.) (Grant EFRI0835878)National Science Foundation (U.S.) (Grant DMS0848804)Society for Neuroscience (Research Award for Innovation in Neuroscience)Wallace H. Coulter FoundationNational Institutes of Health (U.S.) (RO1 MH091220-01)Whitehall FoundationEsther A. & Joseph Klingenstein Fund, Inc.JPB FoundationPIIF FundingNational Institute of Mental Health (U.S.) (R01-MH102441-01)National Institutes of Health (U.S.) (DP2-OD-017366-01)Massachusetts Institute of Technology. Simons Center for the Social Brai

Rapid Effects of Hearing Song on Catecholaminergic Activity in the Songbird Auditory Pathway

Catecholaminergic (CA) neurons innervate sensory areas and affect the processing of sensory signals. For example, in birds, CA fibers innervate the auditory pathway at each level, including the midbrain, thalamus, and forebrain. We have shown previously that in female European starlings, CA activity in the auditory forebrain can be enhanced by exposure to attractive male song for one week. It is not known, however, whether hearing song can initiate that activity more rapidly. Here, we exposed estrogen-primed, female white-throated sparrows to conspecific male song and looked for evidence of rapid synthesis of catecholamines in auditory areas. In one hemisphere of the brain, we used immunohistochemistry to detect the phosphorylation of tyrosine hydroxylase (TH), a rate-limiting enzyme in the CA synthetic pathway. We found that immunoreactivity for TH phosphorylated at serine 40 increased dramatically in the auditory forebrain, but not the auditory thalamus and midbrain, after 15 min of song exposure. In the other hemisphere, we used high pressure liquid chromatography to measure catecholamines and their metabolites. We found that two dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, increased in the auditory forebrain but not the auditory midbrain after 30 min of exposure to conspecific song. Our results are consistent with the hypothesis that exposure to a behaviorally relevant auditory stimulus rapidly induces CA activity, which may play a role in auditory responses

Behavioral state -dependent auditory processing in the avian song system

Many explorations of mammalian systems have indicated that brain functions, particularly sensory processing, are profoundly affected by the animal\u27s behavioral state. The avian song system is an excellent model in which to study behavioral state-dependent regulation of sensory processing in the brain. Because auditory input to the song system is necessary for juvenile song learning, adult song maintenance, and song perception, state-dependent modulation of the ascending flow of auditory information has the potential for significant behavioral impact. Previous studies have suggested that auditory processing in the song system is robust during sleep and anesthesia and predominantly absent during wakefulness. However, little is known about where in the ascending auditory pathway this modulation arises or by what mechanism(s) it occurs. Here we describe dynamic, behavioral state-dependent modulation of auditory responsiveness in the song system nucleus HVC and its auditory afferent NIf and provide evidence for an underlying neuromodulatory mechanism. In contrast to previous studies, we show that both NIf and HVC demonstrate auditory responses during wakefulness. However, while sleeping and anesthetized responses in these areas are stable and narrowly tuned, wakeful responses are smaller, unselective, and variable over time. Using a novel acute recording paradigm in vivo, we also show that auditory responses in NIf and HVC are rapidly co-modulated by arousal state. NIf stains strongly for catecholaminergic innervation and is therefore a candidate site of modulatory action. Using pharmacological manipulations in vivo, we find that norepinephrine (NE) infusion into NIf results in dose-dependent enhancement and suppression of NIf and HVC auditory responsiveness. These effects are mediated by α-adrenergic receptors in NIf. Strikingly, infusion of α-adrenergic antagonists into NIf blocks the behavioral state-dependent modulation of HVC auditory responses. Our results suggest not only that song system auditory responsiveness is robustly modulated by the bird\u27s behavioral state but also that noradrenergic release in NIf is a possible mechanism underlying this state-dependent regulation of auditory processing