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Open Access Publications from the University of California

Scholarly Works (17 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2019)

Neuroanatomical studies play a key role in developing an understanding of neural connectivity and providing insight into how structure leads to function. Cell-type specific tracing methods have been utilized to identify distinct projection neurons originating from the basal forebrain and terminating in the primary visual cortex (V1). These neurons have been exclusively labeled using cell type-specific helper viruses, which allow for selective infection and spread of modified rabies viruses to label the projection neurons terminating onto specific neuron types in V1. While basal forebrain afferents terminate in the infragranular layers of V1, acetylcholine is delivered to more superficial layers through volume transmission. This study was designed to determine the synaptic targets and functional implications of this projection pathway utilizing a retrograde-tracing method to deliver light-gated ion channels to basal forebrain projection neurons. This allowed for direct optogenetic manipulation during single unit recording in V1 of anaesthetized rats. In doing so, we found significant suppression of cell response to the preferred stimulus with basal forebrain activation. Conversely, we found that responses to stimuli smaller than the optimal size were facilitated during basal forebrain activation. Thus, basal forebrain effects on V1 neurons depend on stimulus size. We examine the differences among cortical layers to further distinguish the role acetylcholine plays in the cortex. provide insight into the mechanism of cholinergic modulation from visual processing.

    Cover page: The Role of Neuromodulatory Projections from the Basal Forebrain Area to the Primary Visual Cortex of the Rodent
    • Thesis
    • Peer Reviewed
    UC Irvine Electronic Theses and Dissertations (2019)

    The extrageniculate visual pathway, which carries visual information from the retina through the superficial layers of the superior colliculus and the pulvinar nucleus, is poorly understood. Several studies have implicated this pathway, in particular the pulvinar, in cognitive tasks such as selective attention, but no specific mechanism or circuit has been described that could support such a function. In order to better understand what role this secondary visual pathway serves, here we examine the basic anatomical and functional properties of cells in the pulvinar, and what driving or modulating effect these cells have on visual cortex.

    In the first study, we made extracellular recordings in the pulvinar nucleus of lightly anesthetized rats. We identified visually responsive cells that have large receptive fields on the order of 80 degrees of visual field, fire selectively in response to low spatial frequencies, and can sometimes be selective to the direction or orientation of moving grating stimuli. We also determined that the anatomically-defined lateral subdivision encodes a greater diversity of temporal frequency stimuli than the more medial subdivision, which has better direction selectivity. In the second study, we used modified rabies viruses to retrogradely trace connections between rat pulvinar and visual cortex in order to better understand from where pulvinar receives its visual information and to which cortical areas it is best connected. We found a significantly weaker projection from pulvinar to primary visual cortex (V1) than from pulvinar to higher visual cortex (V2). In the final study, we designed and tested a new modified rabies virus to optically excite and silence populations of the more numerous projections to V2 from the rat pulvinar. We found that pulvinar modulates cortical size tuning and suppresses flash responses, but doesn’t drive activity in V2.

    This dissertation builds a foundational understanding of the role of the pulvinar nucleus in rodents, illustrating how pulvinar integrates spatiotemporal information from visual cortex and the superior colliculus, and regulates firing rates in rodent V2. The new rabies virus variant described here is well suited to test theories of pulvinar function, in addition to its wide potential applications in non-transgenic animals such as cats or non-human primates, where models of pulvinar are already well developed.

      Cover page: Pulvinar contributions to visual cortical processing in the ratCreative Commons 'BY-NC' version 4.0 license
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2021)
      The extrageniculate visual pathway, which carries visual information from the retina through the superficial layers of the superior colliculus and the pulvinar, is poorly understood. The pulvinar is thought to modulate information flow between cortical areas, and has been implicated in cognitive tasks like directing visually guided actions. In order to better understand the underlying circuitry, we performed retrograde injections of modified rabies virus in the visual cortex and pulvinar of the Long-Evans rat. We found a relatively small population of cells projecting to primary visual cortex (V1), compared to a much larger population projecting to higher visual cortex. Reciprocal corticothalamic projections showed a similar result, implying that pulvinar does not play as big a role in directly modulating rodent V1 activity as previously thought.
        Cover page: Projections between visual cortex and pulvinar in the rat
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2017)
        Intrinsic signal optical imaging reveals a highly modular map of orientation preference in the primary visual cortex (V1) of several species. This orientation map is characterized by domains and pinwheels where local circuitry is either more or less orientation selective, respectively. It has now been repeatedly demonstrated that neurons in pinwheels tend to be more broadly tuned to orientation, likely due to the broad range of orientation preference of the neighboring neurons forming pinwheels. However, certain stimulus conditions, such as a decrease in contrast or an increase in size, significantly sharpen tuning widths of V1 neurons. Here, we find that pinwheel neuron tuning widths are broader than domain neurons only for high contrast, optimally sized stimuli, conditions that maximize excitation through feedforward, and local cortical processing. When contrast was lowered or size increased, orientation tuning width sharpened and became equal. These latter conditions are conducive to less local excitation either through lower feedforward drive or by surround suppression arising from long-range cortical circuits. Tuning width differences between pinwheel and domain neurons likely arise through more local circuitry and are overcome through recruitment of longer-range cortical circuits.
          Cover page: Differences in orientation tuning between pinwheel and domain neurons in primary visual cortex depend on contrast and sizeCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2019)
          The basal forebrain provides cholinergic inputs to primary visual cortex (V1) that play a key modulatory role on visual function. While basal forebrain afferents terminate in the infragranular layers of V1, acetylcholine is delivered to more superficial layers through volume transmission. Nevertheless, direct synaptic contact in deep layers 5 and 6 may provide a more immediate effect on V1 modulation. Using helper viruses with cell type specific promoters to target retrograde infection of pseudotyped and genetically modified rabies virus evidence was found for direct synaptic input onto V1 inhibitory neurons. These inputs were similar in number to geniculocortical inputs and, therefore, considered robust. In contrast, while clear evidence for dorsal lateral geniculate nucleus input to V1 excitatory neurons was found, there was no evidence of direct synaptic input from the basal forebrain. These results suggest a direct and more immediate influence of the basal forebrain on local V1 inhibition.
            Cover page: Cell type specific tracing of the subcortical input to primary visual cortex from the basal forebrain
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2022)
            Inherited retinal degenerative diseases are a prominent cause of blindness. Although mutations causing death of photoreceptors are mostly known, the pathophysiology downstream in the inner retina and along the visual pathway is incompletely characterized in the earliest disease stages. Here, we investigated retinal, midbrain and cortical visual function using electroretinography (ERG), the optomotor response (OMR), visual evoked potentials (VEPs), respectively, and single unit electrophysiology at the primary visual cortex (V1) in light-adapted juvenile (approximately one-month-old) and young adult (three-month-old) RhoP23H/WT mice, representative of early-stage retinitis pigmentosa (RP). Photopic ERG revealed up to ∼30% hypersensitivity to light in RhoP23H/WT mice, as measured by the light intensity required to generate half-maximal b-wave (I50 parameter). RhoP23H/WT mice also showed increased OMRs toward low spatial frequency (SF) drifting gratings, indicative of visual overexcitation at the midbrain level. At the V1 level, VEPs and single-cell recordings revealed prominent hyperexcitability in the juvenile RhoP23H/WT mice. Mean VEP amplitudes for light ON stimuli were nearly doubled in one-month-old RhoP23H/WT mice compared with controls, and more than doubled for light OFF. Single-cell recordings showed a significantly increased spontaneous V1 neuron firing in the RhoP23H/WT mice, and persistent contrast and temporal sensitivities. In contrast, direction selectivity was severely compromised. Our data suggest that during early RP, the visual pathway becomes hyperexcited. This could have both compensatory and deleterious consequences for visual behavior. Further studies on the mechanisms of hyperexcitability are warranted as this could lead to therapeutic interventions for RP.
              Cover page: Visual System Hyperexcitability and Compromised V1 Receptive Field Properties in Early-Stage Retinitis Pigmentosa in Mice.
              • Article
              • Peer Reviewed
              UC Irvine Previously Published Works (2020)
              The pulvinar is a higher-order thalamic relay and a central component of the extrageniculate visual pathway, with input from the superior colliculus and visual cortex and output to all of visual cortex. Rodent pulvinar, more commonly called the lateral posterior nucleus (LP), consists of three highly-conserved subdivisions, and offers the advantage of simplicity in its study compared to more subdivided primate pulvinar. Little is known about receptive field properties of LP, let alone whether functional differences exist between different LP subdivisions, making it difficult to understand what visual information is relayed and what kinds of computations the pulvinar might support. Here, we characterized single-cell response properties in two V1 recipient subdivisions of rat pulvinar, the rostromedial (LPrm) and lateral (LPl), and found that a fourth of the cells were selective for orientation, compared to half in V1, and that LP tuning widths were significantly broader. Response latencies were also significantly longer and preferred size more than three times larger on average than in V1; the latter suggesting pulvinar as a source of spatial context to V1. Between subdivisons, LPl cells preferred higher temporal frequencies, whereas LPrm showed a greater degree of direction selectivity and pattern motion detection. Taken together with known differences in connectivity patterns, these results suggest two separate visual feature processing channels in the pulvinar, one in LPl related to higher speed processing which likely derives from superior colliculus input, and the other in LPrm for motion processing derived through input from visual cortex. SIGNIFICANCE STATEMENT: The pulvinar has a perplexing role in visual cognition as no clear link has been found between the functional properties of its neurons and behavioral deficits that arise when it is damaged. The pulvinar, called the lateral posterior nucleus (LP) in rats, is a higher order thalamic relay with input from the superior colliculus and visual cortex and output to all of visual cortex. By characterizing single-cell response properties in anatomically distinct subdivisions we found two separate visual feature processing channels in the pulvinar, one in lateral LP related to higher speed processing which likely derives from superior colliculus input, and the other in rostromedial LP for motion processing derived through input from visual cortex.
                Cover page: Visual Response Characteristics in Lateral and Medial Subdivisions of the Rat Pulvinar
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2014)
                To better reveal the pattern of corticotectal projections to the superficial layers of the superior colliculus (SC), we made a total of ten retrograde tracer injections into the SC of three macaque monkeys (Macaca mulatta). The majority of these injections were in the superficial layers of the SC, which process visual information. To isolate inputs to the purely visual layers in the superficial SC from those inputs to the motor and multisensory layers deeper in the SC, two injections were placed to include the intermediate and deep layers of the SC. In another case, an injection was placed in the medial pulvinar, a nucleus not known to be strongly connected with visual cortex, to identify possible projections from tracer spread past the lateral boundary of the SC. Four conclusions are supported by the results: 1) all early visual areas of cortex, including V1, V2, V3, and the middle temporal area, project to the superficial layers of the SC; 2) with the possible exception of the frontal eye field, few areas of cortex outside of the early visual areas project to the superficial SC, although many do, however, project to the intermediate and deep layers of the SC; 3) roughly matching retinotopy is conserved in the projections of visual areas to the SC; and 4) the projections from different visual areas are similarly dense, although projections from early visual areas appear somewhat denser than those of higher order visual areas in macaque cortex.
                  Cover page: Distribution of cortical neurons projecting to the superior colliculus in macaque monkeys
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2022)
                  Despite the fundamental importance of understanding the brain's wiring diagram, our knowledge of how neuronal connectivity is rewired by traumatic brain injury remains remarkably incomplete. Here we use cellular resolution whole-brain imaging to generate brain-wide maps of the input to inhibitory neurons in a mouse model of traumatic brain injury. We find that somatostatin interneurons are converted into hyperconnected hubs in multiple brain regions, with rich local network connections but diminished long-range inputs, even at areas not directly damaged. The loss of long-range input does not correlate with cell loss in distant brain regions. Interneurons transplanted into the injury site receive orthotopic local and long-range input, suggesting the machinery for establishing distant connections remains intact even after a severe injury. Our results uncover a potential strategy to sustain and optimize inhibition after traumatic brain injury that involves spatial reorganization of the direct inputs to inhibitory neurons across the brain.
                    Cover page: Brain-wide reconstruction of inhibitory circuits after traumatic brain injury
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2014)
                    Neurons in primary visual cortex (V1) integrate across the representation of the visual field through networks of long-range projecting pyramidal neurons. These projections, which originate from within V1 and through feedback from higher visual areas, are likely to play a key role in such visual processes as low contrast facilitation and extraclassical surround suppression. The extent of the visual field representation covered by feedback is generally much larger than that covered through monosynaptic horizontal connections within V1, and, although it may be possible that multisynaptic horizontal connections across V1 could also lead to more widespread spatial integration, nothing is known regarding such circuits. In this study, we used injections of the CVS-11 strain of rabies virus to examine disynaptic long-range horizontal connections within macaque monkey V1. Injections were made around the representation of 5° eccentricity in the lower visual field. Along the opercular surface of V1, we found that the majority of connected neurons extended up to 8 mm in most layers, consistent with twice the typically reported distances of monosynaptic connections. In addition, mainly in layer 6, a steady presence of connected neurons within V1 was observed up to 16 mm away. A relatively high percentage of these connected neurons had large-diameter somata characteristic of Meynert cells, which are known to project as far as 8 mm individually. Several neurons, predominantly in layer 6, were also found deep within the calcarine sulcus, reaching as far as 20° of eccentricity, based on estimates, and extending well into the upper visual field representation. Thus, our anatomical results provide evidence for a wide-ranging disynaptic circuit within V1, mediated largely through layer 6, that accounts for integration across a large region of the visual field.
                      Cover page: Very-long-range disynaptic V1 connections through layer 6 pyramidal neurons revealed by transneuronal tracing with rabies virus.
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