Na+ channels enhance low contrast signalling in the superior-coding direction-selective circuit

dc.contributor.authorMcLaughlin, Amanda J.
dc.contributor.supervisorTaylor, John Stewart Neuroscienceen_US of Philosophy Ph.D.en_US
dc.description.abstractLight entering the eye is transformed by the retina into electrical signals. Extensive processing takes place in the retina before these signals are transmitted to the brain. Beginning in the outer retina, light-evoked electrical signals are distributed into parallel pathways specialized for different visual tasks, such as the detection of dark vs. bright ambient light, the onset or offset of light, and the direction of stimulus motion. Pathway diversity is a consequence of cell type diversity, differential cell connectivity, synapse organization, receptor expression, or any combination thereof. Cell connectivity itself can be accomplished through excitatory or inhibitory chemical synapses, or electrical coupling via gap junctions. Gap junctions are further specialized based on the expression of different connexin subunit isoforms. In aggregate, this diversity gives rise to ganglion cells with highly specialized functions, including ON and/or OFF responses, contrast-tuning and direction-selectivity (DS). The directionally-selective circuit, a circuit specialized for the encoding of stimulus motion, makes use of many of these circuit specializations. Bipolar cells, in response to glutamate release from cone photoreceptors, provide highly-sensitive glutamatergic input to amacrine cells and DS ganglion cells (DSGCs) in this circuit, while amacrine cells provide cholinergic and directionally-tuned GABAergic input to DSGCs. One population of DSGCs also transmit signals laterally to one another via gap junctions. Thus numerous specializations in bipolar cells, amacrine cells and ganglion cells endow DSGCs with their unique encoding abilities. In Chapters 2 and 3 of this dissertation I focus on synchronized firing between gap junction-coupled DSGCs. sDSGCs exhibit fine-scale correlations, with action potentials in an sDSGC more likely within ~2ms of action potential firing in a coupled neighbour. I first characterize electrical coupling of DSGCs through the identification of the molecular composition of DSGC gap junctions (Chapter 2). Physiological and immunohistochemical methods allowed me to demonstrate an important role for connexin 36 subunits in DSGC electrical coupling. Next (Chapter 3) I investigate the sub-cellular mechanisms underlying neuronal correlations between electrically coupled DSGCs. Using paired recordings, I show that chemical input (from bipolar cells and amacrine cells), electrical input (from gap junctions), and Na+ channel activity in DSGC dendrites underlie the generation of correlated spiking activity. While a common feature of electrically coupled networks, the mechanisms underlying correlations were previously unclear. In Chapter 4 I focus on the mechanisms within the DS circuit that endow these neurons with impressive sensitivity to stimulus contrast. Using physiological and pharmacological methods I first assess the relative contrast sensitivity of ganglion cells and starburst amacrine cells (SACs) in the DS circuit. The sensitivity of DSGC and SAC excitatory currents to antagonists of Na+ channels suggests an important role for these channels in amplifying low contrast responses and other weak inputs to the circuit. This role is later attributed to the differential expression of voltage-gated Na+ channels in specific bipolar cell populations. In aggregate, this dissertation describes several novel circuit mechanisms within the well-studied DS circuit. I also provide specific roles for such specializations in visual coding.en_US
dc.identifier.bibliographicCitationSethuramanujam, S., McLaughlin, AJ., DeRosenroll, G., Hoggarth, A., Schwab, D.J. & Awatramani, GA. (2016). A central role for mixed acetylcholine/GABA transmission in direction coding in the retina. Neuron. 90(6):1243-1256.en_US
dc.identifier.bibliographicCitationHoggarth, A., McLaughlin, AJ., Ronellenfitch, K., Trenholm, S., Vasandani, R., Sethuramanujam, S., Schwab, D., Briggman, KL., Awatramani, GB. (2015). Specific wiring of distinct amacrine cells in the directionally selective retinal circuit permits independent coding of direction and size. Neuron. 86(1):276-91en_US
dc.identifier.bibliographicCitationMcLaughlin, A.J.*, Trenholm S.*, Schwab, D.J., Turner, M.H., Smith, R.G., Rieke, F., Awatramani, G.B. (2014). Nonlinear dendritic integration of electrical and chemical synaptic inputs mediates fine-scale neural correlations. Nature Neuroscience. 17(12):1759-66 (*co-first authors).en_US
dc.identifier.bibliographicCitationTrenholm S., McLaughlin, AJ., Schwab, D., Awatramani, GB. (2013). Dynamic tuning of electrical and chemical synaptic transmission in a network of motion coding retinal neurons. The Journal of Neuroscience. 33(37):14927-38en_US
dc.rightsAvailable to the World Wide Weben_US
dc.subjectganglion cellen_US
dc.subjectgap junctionen_US
dc.subjectcontrast sensitivityen_US
dc.subjectSodium channelen_US
dc.subjectNa+ channelen_US
dc.subjectbipolar cellen_US
dc.subjectdendritic spikeen_US
dc.subjectfine-scale correlationsen_US
dc.titleNa+ channels enhance low contrast signalling in the superior-coding direction-selective circuiten_US


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