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Open Access Publications from the University of California

Scholarly Works (38 results)

  • Article
LBL Publications (1993)
    Cover page: Coadjoint Orbits and Conformal Field Theory
    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2016)
    Neurons that signal the orientation of edges within the visual field have been widely studied in primary visual cortex. Much less is known about the mechanisms of orientation selectivity that arise earlier in the visual stream. Here we examine the synaptic and morphological properties of a subtype of orientation-selective ganglion cell in the rabbit retina. The receptive field has an excitatory ON center, flanked by excitatory OFF regions, a structure similar to simple cell receptive fields in primary visual cortex. Examination of the light-evoked postsynaptic currents in these ON-type orientation-selective ganglion cells (ON-OSGCs) reveals that synaptic input is mediated almost exclusively through the ON pathway. Orientation selectivity is generated by larger excitation for preferred relative to orthogonal stimuli, and conversely larger inhibition for orthogonal relative to preferred stimuli. Excitatory orientation selectivity arises in part from the morphology of the dendritic arbors. Blocking GABAA receptors reduces orientation selectivity of the inhibitory synaptic inputs and the spiking responses. Negative contrast stimuli in the flanking regions produce orientation-selective excitation in part by disinhibition of a tonic NMDA receptor-mediated input arising from ON bipolar cells. Comparison with earlier studies of OFF-type OSGCs indicates that diverse synaptic circuits have evolved in the retina to detect the orientation of edges in the visual input.

    Significance statement

    A core goal for visual neuroscientists is to understand how neural circuits at each stage of the visual system extract and encode features from the visual scene. This study documents a novel type of orientation-selective ganglion cell in the retina and shows that the receptive field structure is remarkably similar to that of simple cells in primary visual cortex. However, the data indicate that, unlike in the cortex, orientation selectivity in the retina depends on the activity of inhibitory interneurons. The results further reveal the physiological basis for feature detection in the visual system, elucidate the synaptic mechanisms that generate orientation selectivity at an early stage of visual processing, and illustrate a novel role for NMDA receptors in retinal processing.
      Cover page: Synaptic Mechanisms Generating Orientation Selectivity in the ON Pathway of the Rabbit Retina
      • Article
      • Peer Reviewed
      Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health, Volume 17, Issue 1 (2016)

      Introduction: Little is known about the frequency and locations in which emergency physicians (EPs) are bystanders to an accident or emergency; equally uncertain is which contents of an “emergency kit” may be useful during such events. The aim of this study was to describe the frequency and locations of Good Samaritan acts by EPs and also determine which emergency kit supplies and medications were most commonly used by Good Samaritans.

      Methods: We conducted an electronic survey among a convenience sample of EPs in Colorado.

      Results: Respondents reported a median frequency of 2.0 Good Samaritan acts per five years of practice, with the most common locations being sports and entertainment events (25%), road traffic accidents (21%), and wilderness settings (19%). Of those who had acted as Good Samaritans, 86% reported that at least one supply would have been useful during the most recent event, and 66% reported at least one medication would have been useful. The most useful supplies were gloves (54%), dressings (34%), and a stethoscope (20%), while the most useful medications were oxygen (19%), intravenous fluids (17%), and epinephrine (14%).

      Conclusion: The majority of EPs can expect to provide Good Samaritan care during their careers and would be better prepared by carrying a kit with common supplies and medications where they are most likely to use them.

        Cover page: Emergency Physicians as Good Samaritans: Survey of Frequency, Locations, Supplies and MedicationsCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2015)
        Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene.
          Cover page: The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal Amacrine Cell of the Rabbit Retina
          • Thesis
          • Peer Reviewed
          UC Riverside Electronic Theses and Dissertations (2018)

          Semicompatibilism is the view that the freedom required for moral responsibility is compatible with causal determinism even if the freedom to do otherwise is not. I address five main objections to semicompatibilism in my thesis, defending the view against all charges. Because the view is a compatibilist one, it is targeted by objections to compatibilism itself. I focus on two sets of objections: the manipulation objection and two objections from luck. I argue that compatibilist views are safe from both sets of objections. I then consider two objections that target semicompatibilism in particular. The first challenges the view’s distinctiveness, claiming that the dispute between semicompatibilists and traditional compatibilists is merely verbal. The second objection challenges proponents of semicompatibilism to provide an adequate account of moral responsibility for omissions. In addressing each objection, I aim not only to defend semicompatibilism but also to clarify the nature of moral responsibility itself. In particular, I develop and defend three novel views: 1) that one's history can affect the degree to which one is morally responsible, 2) that indeterminacy is no gain to the control necessary for moral responsibility, and 3) that the requirements on moral responsibility for actions and omissions are symmetrical.

            Cover page: Semicompatibilist Options: Essays in Defense of an Actual-Sequence Approach to Freedom and Responsibility
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2012)
            Different types of retinal ganglion cells represent distinct spatiotemporal filters that respond selectively to specific features in the visual input. Much about the circuitry and synaptic mechanisms that underlie such specificity remains to be determined. This study examines how N-methyl-d-aspartate (NMDA) receptor signaling combines with other excitatory and inhibitory mechanisms to shape the output of small-field OFF brisk-sustained ganglion cells (OFF-BSGCs) in the rabbit retina. We used voltage clamp to separately resolve NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and inhibitory inputs elicited by stimulation of the receptive field center. Three converging circuits were identified. First is a direct glutamatergic input, arising from OFF cone bipolar cells (CBCs), which is mediated by synaptic NMDA and AMPA receptors. The NMDA input was saturated at 10% contrast, whereas the AMPA input increased monotonically up to 60% contrast. We propose that NMDA inputs selectively enhance sensitivity to low contrasts. The OFF bipolar cells, mediating this direct excitatory input, express dendritic kainate (KA) receptors, which are resistant to the nonselective AMPA/KA receptor antagonist, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium salt (NBQX), but are suppressed by a GluK1- and GluK3-selective antagonist, (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxy-thiophene-3-yl-methyl)-5-methylpyrimidine-2,4-dione (UBP-310). The second circuit entails glycinergic crossover inhibition, arising from ON-CBCs and mediated by AII amacrine cells, which modulate glutamate release from the OFF-CBC terminals. The third circuit also comprises glycinergic crossover inhibition, which is driven by the ON pathway; however, this inhibition impinges directly on the OFF-BSGCs and is mediated by an unknown glycinergic amacrine cell that expresses AMPA but not KA receptors.
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2016)
              There is considerable debate whether Alzheimer's disease (AD) originates in basal forebrain or entorhinal cortex. Here we examined whether longitudinal decreases in basal forebrain and entorhinal cortex grey matter volume were interdependent and sequential. In a large cohort of age-matched older adults ranging from cognitively normal to AD, we demonstrate that basal forebrain volume predicts longitudinal entorhinal degeneration. Models of parallel degeneration or entorhinal origin received negligible support. We then integrated volumetric measures with an amyloid biomarker sensitive to pre-symptomatic AD pathology. Comparison between cognitively matched normal adult subgroups, delineated according to the amyloid biomarker, revealed abnormal degeneration in basal forebrain, but not entorhinal cortex. Abnormal degeneration in both basal forebrain and entorhinal cortex was only observed among prodromal (mildly amnestic) individuals. We provide evidence that basal forebrain pathology precedes and predicts both entorhinal pathology and memory impairment, challenging the widely held belief that AD has a cortical origin.
                Cover page: Basal forebrain degeneration precedes and predicts the cortical spread of Alzheimer’s pathology
                • Article
                • Peer Reviewed
                UC Berkeley Previously Published Works (2019)
                Two types of mammalian direction-selective ganglion cells (DSGCs), ON and ONOFF, operate over different speed ranges. The directional axes of the ON-DSGCs are thought to align with the axes of the vestibular system and provide sensitivity at rotational velocities that are too slow to activate the semicircular canals. ONOFF-DSGCs respond to faster image velocities. Using natural images that simulate the natural visual inputs to freely moving animals, we show that simulated visual saccades suppress responses in ON-DSGCs but not ONOFF-DSGCs recorded in retinas of domestic rabbits of either gender. Analysis of the synaptic inputs shows that this saccadic suppression results from glycinergic inputs that are specific to ON-DSGCs and are absent in ONOFF-DSGCs. When this glycinergic input is blocked, both cell types respond similarly to visual saccades and display essentially identical speed tuning. The results demonstrate that glycinergic circuits within the retina can produce saccadic suppression of retinal ganglion cell activity. The cell-type-specific targeting of the glycinergic circuits further supports the proposed physiological roles of ON-DSGCs in retinal-image stabilization and of ONOFF-DSGCs in detecting local object motion and signaling optical flow.SIGNIFICANCE STATEMENT In the mammalian retina, ON direction-selective ganglion cells (DSGCs) respond preferentially to slow image motion, whereas ONOFF-DSGCs respond better to rapid motion. The mechanisms producing this different speed tuning remain unclear. Here we show that simulated visual saccades suppress ON-DSGCs, but not ONOFF-DSGCs. This selective saccadic suppression is because of the selective targeting of glycinergic inhibitory synaptic inputs to ON-DSGCs. The different saccadic suppression in the two cell types points to different physiological roles, consistent with their projections to distinct areas within the brain. ON-DSGCs may be critical for providing the visual feedback signals that contribute to stabilizing the image on the retina, whereas ONOFF-DSGCs may be important for detecting the onset of saccades or for signaling optical flow.
                  Cover page: Simulated Saccadic Stimuli Suppress ON-Type Direction-Selective Retinal Ganglion Cells via Glycinergic Inhibition
                  • Article
                  • Peer Reviewed
                  UC Berkeley Previously Published Works (2019)
                  Directional responses in retinal ganglion cells are generated in large part by direction-selective release of γ-aminobutyric acid from starburst amacrine cells onto direction-selective ganglion cells (DSGCs). The excitatory inputs to DSGCs are also widely reported to be direction-selective, however, recent evidence suggests that glutamate release from bipolar cells is not directional, and directional excitation seen in patch-clamp analyses may be an artifact resulting from incomplete voltage control. Here, we test this voltage-clamp-artifact hypothesis in recordings from 62 ON-OFF DSGCs in the rabbit retina. The strength of the directional excitatory signal varies considerably across the sample of cells, but is not correlated with the strength of directional inhibition, as required for a voltage-clamp artifact. These results implicate additional mechanisms in generating directional excitatory inputs to DSGCs.
                    Cover page: Directional excitatory input to direction‐selective ganglion cells in the rabbit retina
                    • Article
                    • Peer Reviewed
                    UC Berkeley Previously Published Works (2011)
                    Detailed analysis of the synaptic inputs to the primate DB1 bipolar cell has been precluded by the absence of a suitable immunohistochemical marker. Here we demonstrate that antibodies for the EF-hand calcium-binding protein, secretagogin, strongly label the DB1 bipolar cell as well as a mixed population of GABAergic amacrine cells in the macaque retina. Using secretagogin as a marker, we show that the DB1 bipolar makes synaptic contact with both L/M as well as S-cone photoreceptors and only minimal contact with rod photoreceptors. Electron microscopy showed that the DB1 bipolar makes flat contacts at both triad-associated and nontriad-associated positions on the cone pedicle. Double labeling with various glutamate receptor subunit antibodies failed to conclusively determine the subunit composition of the glutamate receptors on DB1 bipolar cells. In the IPL, DB1 bipolar cell axon terminals expressed the glycine receptor, GlyRα1, at sites of contact with AII amacrine cells, suggesting that these cells receive input from the rod pathway.
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