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Open Access Publications from the University of California

Scholarly Works (18 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2015)
There has been a surge of interest in how inhibitory neurons influence the output of local circuits in the brain. In this issue of Neuron, Scholl et al. (2015) provide a compelling argument for what one class of inhibitory neurons actually does.
    Cover page: Parvalbumin Interneurons: All Forest, No Trees
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2015)
    Maturation of cortical inhibition just after eye opening is a necessary precedent for the emergence of competitive, experience-dependent ocular dominance plasticity in the visual cortex. What inhibition is doing in this context, though, is not clear. Here I outline new hypotheses on the roles of somatic and dendritic inhibition in the opening and closure of critical periods, and their roles in the competitive processes therein.
      Cover page: Competition, inhibition, and critical periods of cortical plasticity
      • Thesis
      • Peer Reviewed
      UCLA Electronic Theses and Dissertations (2014)

      Adequate perisomatic inhibition in the cortex, as supplied by parvalbumin-expressing (PV) inhibitory neurons, is fundamental to critical period plasticity and cortical function. Yet, how perisomatic inhibition emerges just at the inception of the critical period to shape the structure and function of cortical circuits is little understood. We report that PTEN in PV cells serves as a regulator of perisomatic inhibition by controlling the expression of EphB4, an inhibitor of PV to pyramidal inhibitory synapse formation. This points to a molecular disinhibitory mechanism for the initiation of the critical period, whereby sensory experience acts on PTEN in PV cells to decrease EphB4 expression in order to reduce the native repulsion between PV presynaptic terminals and pyramidal neuron cell bodies. This would then permit the formation of adequate perisomatic inhibition in cortical circuits. Given the compelling link between deficits in cortical perisomatic inhibition and various psychiatric disorders, such as autism spectrum disorders and schizophrenia, our findings also recommend EphB4 in PV cells as a novel target of therapy.

        Cover page: PTEN and the Emergence of Cortical Perisomatic Inhibition
        • Thesis
        • Peer Reviewed
        UCLA Electronic Theses and Dissertations (2018)

        During so-called critical periods of early postnatal life, sensory experience profoundly and permanently sculpts cortical neural circuitry. After critical period closure, experience-dependent plasticity is dramatically limited, and it is not known what differentiates juvenile and adult plasticity mechanisms. At its core, plasticity is a dendritic phenomenon, and in the cortex, plasticity is determined by changes in sensory input and cortical state. Here we show that dendritic and somatic activity in pyramidal neurons is fundamentally different across critical period closure due to the cholinergic engagement of inhibitory circuitry. At the peak of the critical period, acetylcholine released from the basal forebrain directly excites somatostatin-expressing (SST) interneurons. The resultant inhibition of pyramidal cell dendrites and of fast-spiking, parvalbumin-expressing (PV) inhibitory neurons enhances branch-specific dendritic responses and increases somatic spiking within pyramidal neurons. By adulthood, SST cells lose cholinergic excitability, and inhibition becomes inverted along the somatodendritic axis, with less SST-mediated dendritic inhibition and more PV-mediated somatic inhibition. When SST cells are optogenetically activated in adult cortex, branch-specific dendritic activity and somatic disinhibition re-emerge. Conversely, suppressing SST cell activity during the critical period prevents the normal development of binocular receptive fields by impairing the experience-dependent maturation of ipsilateral eye inputs. These data reveal a transient circuit through which inhibition and neuromodulation converge to facilitate experience-dependent plasticity by shaping dendritic and somatic activity.

          Cover page: A transient microcircuit underlying critical period plasticity in the visual cortex
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2019)
          Sensory experience in early postnatal life, during so-called critical periods, restructures neural circuitry to enhance information processing1. Why the cortex is susceptible to sensory instruction in early life and why this susceptibility wanes with age are unclear. Here we define a developmentally restricted engagement of inhibitory circuitry that shapes localized dendritic activity and is needed for vision to drive the emergence of binocular visual responses in the mouse primary visual cortex. We find that at the peak of the critical period for binocular plasticity, acetylcholine released from the basal forebrain during periods of heightened arousal directly excites somatostatin (SST)-expressing interneurons. Their inhibition of pyramidal cell dendrites and of fast-spiking, parvalbumin-expressing interneurons enhances branch-specific dendritic responses and somatic spike rates within pyramidal cells. By adulthood, this cholinergic sensitivity is lost, and compartmentalized dendritic responses are absent but can be re-instated by optogenetic activation of SST cells. Conversely, suppressing SST cell activity during the critical period prevents the normal development of binocular receptive fields by impairing the maturation of ipsilateral eye inputs. This transient cholinergic modulation of SST cells, therefore, seems to orchestrate two features of neural plasticity-somatic disinhibition and compartmentalized dendritic spiking. Loss of this modulation may contribute to critical period closure.
            Cover page: Neuromodulatory control of localized dendritic spiking in critical period cortex.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2022)
            The mouse primary visual cortex is a model system for understanding the relationship between cortical structure, function, and behavior (Seabrook et al., 2017; Chaplin and Margrie, 2020; Hooks and Chen, 2020; Saleem, 2020; Flossmann and Rochefort, 2021). Binocular neurons in V1 are the cellular basis of binocular vision, which is required for predation (Scholl et al., 2013; Hoy et al., 2016; La Chioma et al., 2020; Berson, 2021; Johnson et al., 2021). The normal development of binocular responses, however, has not been systematically measured. Here, we measure tuning properties of neurons to either eye in awake mice of either sex from eye opening to the closure of the critical period. At eye opening, we find an adult-like fraction of neurons responding to the contralateral-eye stimulation, which are selective for orientation and spatial frequency; few neurons respond to ipsilateral eye, and their tuning is immature. Fraction of ipsilateral-eye responses increases rapidly in the first few days after eye opening and more slowly thereafter, reaching adult levels by critical period closure. Tuning of these responses improves with a similar time course. The development and tuning of binocular responses parallel that of ipsilateral-eye responses. Four days after eye opening, monocular neurons respond to a full range of orientations but become more biased to cardinal orientations. Binocular responses, by contrast, lose their cardinal bias with age. Together, these data provide an in-depth accounting of the development of monocular and binocular responses in the binocular region of mouse V1 using a consistent set of visual stimuli and measurements.SIGNIFICANCE STATEMENT In this manuscript, we present a full accounting of the emergence and refinement of monocular and binocular receptive field tuning properties of thousands of pyramidal neurons in mouse primary visual cortex. Our data reveal new features of monocular and binocular development that revise current models on the emergence of cortical binocularity. Given the recent interest in visually guided behaviors in mice that require binocular vision (e.g., predation), our measures will provide the basis for studies on the emergence of the neural circuitry guiding these behaviors.
              Cover page: The Development of Receptive Field Tuning Properties in Mouse Binocular Primary Visual Cortex.
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2016)

              Unlabelled

              We do not fully understand how behavioral state modulates the processing and transmission of sensory signals. Here, we studied the cortical representation of the retinal image in mice that spontaneously switched between a state of rest and a constricted pupil, and one of active locomotion and a dilated pupil, indicative of heightened attention. We measured the selectivity of neurons in primary visual cortex for orientation and spatial frequency, as well as their response gain, in these two behavioral states. Consistent with prior studies, we found that preferred orientation and spatial frequency remained invariant across states, whereas response gain increased during locomotion relative to rest. Surprisingly, relative gain, defined as the ratio between the gain during locomotion and the gain during rest, was not uniform across the population. Cells tuned to high spatial frequencies showed larger relative gain compared with those tuned to lower spatial frequencies. The preferential enhancement of high-spatial-frequency information was also reflected in our ability to decode the stimulus from population activity. Finally, we show that changes in gain originate from shifts in the operating point of neurons along a spiking nonlinearity as a function of behavioral state. Differences in the relative gain experienced by neurons with high and low spatial frequencies are due to corresponding differences in how these cells shift their operating points between behavioral states.

              Significance statement

              How behavioral state modulates the processing and transmission of sensory signals remains poorly understood. Here, we show that the mean firing rate and neuronal gain increase during locomotion as a result in a shift of the operating point of neurons. We define relative gain as the ratio between the gain of neurons during locomotion and rest. Interestingly, relative gain is higher in cells with preferences for higher spatial frequencies than those with low-spatial-frequency selectivity. This means that, during a state of locomotion and heightened attention, the population activity in primary visual cortex can support better spatial acuity, a phenomenon that parallels the improved spatial resolution observed in human subjects during the allocation of spatial attention.
                Cover page: Enhanced Spatial Resolution During Locomotion and Heightened Attention in Mouse Primary Visual Cortex
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2013)
                Early sensory experience instructs the maturation of neural circuitry in the cortex. This has been studied extensively in the primary visual cortex, in which loss of vision to one eye permanently degrades cortical responsiveness to that eye, a phenomenon known as ocular dominance plasticity (ODP). Cortical inhibition mediates this process, but the precise role of specific classes of inhibitory neurons in ODP is controversial. Here we report that evoked firing rates of binocular excitatory neurons in the primary visual cortex immediately drop by half when vision is restricted to one eye, but gradually return to normal over the following twenty-four hours, despite the fact that vision remains restricted to one eye. This restoration of binocular-like excitatory firing rates after monocular deprivation results from a rapid, although transient, reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) interneurons, which in turn can be attributed to a decrease in local excitatory circuit input onto PV interneurons. This reduction in PV-cell-evoked responses after monocular lid suture is restricted to the critical period for ODP and appears to be necessary for subsequent shifts in excitatory ODP. Pharmacologically enhancing inhibition at the time of sight deprivation blocks ODP and, conversely, pharmacogenetic reduction of PV cell firing rates can extend the critical period for ODP. These findings define the microcircuit changes initiating competitive plasticity during critical periods of cortical development. Moreover, they show that the restoration of evoked firing rates of layer 2/3 pyramidal neurons by PV-specific disinhibition is a key step in the progression of ODP.
                  Cover page: A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2021)
                  Depth perception emerges from the development of binocular neurons in primary visual cortex. Vision is required for these neurons to acquire their mature responses to visual stimuli. The prevailing view is that vision does not influence binocular circuitry until the onset of the critical period, about a week after eye opening, and that plasticity of visual responses is triggered by increased inhibition. Here, we show that vision is required to form binocular neurons and to improve binocular tuning and matching from eye opening until critical period closure. Enhancing inhibition does not accelerate this process. Vision soon after eye opening improves the tuning properties of binocular neurons by strengthening and sharpening ipsilateral eye cortical responses. This progressively changes the population of neurons in the binocular pool, and this plasticity is sensitive to interocular differences prior to critical period onset. Thus, vision establishes binocular circuitry and guides binocular plasticity from eye opening.
                    Cover page: Vision is required for the formation of binocular neurons prior to the classical critical period
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2020)
                    High acuity stereopsis emerges during an early postnatal critical period when binocular neurons in the primary visual cortex sharpen their receptive field tuning properties. We find that this sharpening is achieved by dismantling the binocular circuit present at critical period onset and building it anew. Longitudinal imaging of receptive field tuning (e.g., orientation selectivity) of thousands of neurons reveals that most binocular neurons present in layer 2/3 at critical period onset are poorly tuned and are rendered monocular. In parallel, new binocular neurons are established by conversion of well-tuned monocular neurons as they gain matched input from the other eye. These improvements in binocular tuning in layer 2/3 are not inherited from layer 4 but are driven by the experience-dependent sharpening of ipsilateral eye responses. Thus, vision builds a new and more sharply tuned binocular circuit in layer 2/3 by cellular exchange and not by refining the original circuit.
                      Cover page: Vision Changes the Cellular Composition of Binocular Circuitry during the Critical Period
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