8
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      State-Dependent Subnetworks of Parvalbumin-Expressing Interneurons in Neocortex

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          SUMMARY

          Brain state determines patterns of spiking output that underlie behavior. In neocortex, brain state is reflected in the spontaneous activity of the network, which is regulated in part by neuromodulatory input from the brain stem and by local inhibition. We find that fast-spiking, parvalbumin-expressing inhibitory neurons, which exert state-dependent control of network gain and spike patterns, cluster into two stable and functionally distinct subnetworks that are differentially engaged by ascending neuromodulation. One group is excited as a function of increased arousal state; this excitation is driven in part by the increase in cortical norepinephrine that occurs when the locus coeruleus is active. A second group is suppressed during movement when acetylcholine is released into the cortex via projections from the nucleus basalis. These data establish the presence of functionally independent subnetworks of Parvalbumin (PV) cells in the upper layers of the neocortex that are differentially engaged by the ascending reticular activating system.

          Graphical Abstract

          In Brief

          Fast-spiking interneurons in cortex are generally viewed as functionally homogeneous. Garcia-Junco-Clemente et al. present evidence that across diverse cortical areas there are at least two functionally distinct subnetworks of these interneurons, which can be independently engaged as a function of behavior.

          Related collections

          Most cited references19

          • Record: found
          • Abstract: found
          • Article: not found

          Interneuron cell types are fit to function.

          Understanding brain circuits begins with an appreciation of their component parts - the cells. Although GABAergic interneurons are a minority population within the brain, they are crucial for the control of inhibition. Determining the diversity of these interneurons has been a central goal of neurobiologists, but this amazing cell type has so far defied a generalized classification system. Interneuron complexity within the telencephalon could be simplified by viewing them as elaborations of a much more finite group of developmentally specified cardinal classes that become further specialized as they mature. Our perspective emphasizes that the ultimate goal is to dispense with classification criteria and directly define interneuron types by function.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Cortical interneurons that specialize in disinhibitory control

            In the mammalian cerebral cortex, the diversity of interneuronal subtypes underlies a division of labor subserving distinct modes of inhibitory control 1–7 . A unique mode of inhibitory control may be provided by inhibitory neurons that specifically suppress the firing of other inhibitory neurons. Such disinhibition could lead to the selective amplification of local processing and serve the important computational functions of gating and gain modulation 8,9 . Although several interneuron populations are known to target other interneurons to varying degrees 10–15 , little is known about interneurons specializing in disinhibition and their in vivo function. Here we show that a class of interneurons that express vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of neocortex and is recruited by reinforcement signals. By combining optogenetic activation with single cell recordings, we examined the functional role of VIP interneurons in awake mice, and investigated the underlying circuit mechanisms in vitro in auditory and medial prefrontal cortices. We identified a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons that specialize in the control of the input and output of principal cells, respectively 3,6,16,17 . During the performance of an auditory discrimination task, reinforcement signals (reward and punishment) strongly and uniformly activated VIP neurons in auditory cortex, and in turn VIP recruitment increased the gain of a functional subpopulation of principal neurons. These results reveal a specific cell-type and microcircuit underlying disinhibitory control in cortex and demonstrate that it is activated under specific behavioural conditions.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Pupil fluctuations track fast switching of cortical states during quiet wakefulness.

              Neural responses are modulated by brain state, which varies with arousal, attention, and behavior. In mice, running and whisking desynchronize the cortex and enhance sensory responses, but the quiescent periods between bouts of exploratory behaviors have not been well studied. We found that these periods of "quiet wakefulness" were characterized by state fluctuations on a timescale of 1-2 s. Small fluctuations in pupil diameter tracked these state transitions in multiple cortical areas. During dilation, the intracellular membrane potential was desynchronized, sensory responses were enhanced, and population activity was less correlated. In contrast, constriction was characterized by increased low-frequency oscillations and higher ensemble correlations. Specific subtypes of cortical interneurons were differentially activated during dilation and constriction, consistent with their participation in the observed state changes. Pupillometry has been used to index attention and mental effort in humans, but the intracellular dynamics and differences in population activity underlying this phenomenon were previously unknown.
                Bookmark

                Author and article information

                Journal
                101573691
                39703
                Cell Rep
                Cell Rep
                Cell reports
                2211-1247
                4 March 2019
                26 February 2019
                08 March 2019
                : 26
                : 9
                : 2282-2288.e3
                Affiliations
                [1 ]Department of Neurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
                [2 ]Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla and Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, and CIBERNED, Seville, Spain
                [3 ]Department of Psychology, University of California, Los Angeles, Los Angeles, CA 90095, USA
                [4 ]Lead Contact
                Author notes
                [* ]Correspondence: pgarciajunco@ 123456gmail.com

                AUTHOR CONTRIBUTIONS

                P.G.-J.-C. and J.T.T. conceived the study, analyzed the data, wrote the manuscript, and prepared the figures. P.G.-J.-C. collected the data presented in Figures 1, 2, 4, S1, and S2. E.T. collected the data presented in Figure 3. D.L.R. provided the MATLAB analysis code as well as all of the code for data acquisition via 2-photon microscopy.

                Article
                NIHMS1522761
                10.1016/j.celrep.2019.02.005
                6407626
                30811979
                87c2dacc-4ee6-4f0d-8be1-3b33799197ad

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Article

                Cell biology
                Cell biology

                Comments

                Comment on this article