Distinct roles for inhibition in spatial and temporal tuning of local edge detectors in the rabbit retina.

This paper examines the role of inhibition in generating the receptive-field properties of local edge detector (LED) ganglion cells in the rabbit retina. We confirm that the feed-forward inhibition is largely glycinergic but, contrary to a recent report, our data demonstrate that the glycinergic inhibition contributes to temporal tuning for the OFF and ON inputs to the LEDs by delaying the onset of spiking; this delay was more pronounced for the ON inputs (∼ 340 ms) than the OFF inputs (∼ 12 ms). Blocking glycinergic transmission reduced the delay to spike onset and increased the responses to flickering stimuli at high frequencies. Analysis of the synaptic conductances indicates that glycinergic amacrine cells affect temporal tuning through both postsynaptic inhibition of the LEDs and presynaptic modulation of the bipolar cells that drive the LEDs. The results also confirm that presynaptic GABAergic transmission contributes significantly to the concentric surround antagonism in LEDs; however, unlike presumed LEDs in the mouse retina, the surround is only partly generated by spiking amacrine cells

Physiology and Anatomy of rarely encountered ganglion cells in the mammalian retina

There are about 15-20 types of retinal ganglion cells (RGCs), each providing a filtered representation of the visual input to the brain. The diverse receptive-field properties of different types of RGCs are formed by the retinal interneurons that provide the synaptic input, including 10–12 types of excitatory bipolar cells and 40–50 types of inhibitory amacrine cells. Many of the RGCs have a concentric organization, with an ON-center and OFF-surround or vice versa, and there is a good understanding of how their receptive fields are generated. However, much remains to be discovered about the synaptic mechanisms that underlie the responses of other RGCs with complex receptive-field properties. In this thesis, I have studied several types of complex RGCs that are rarely encountered, including the uniformity detector (UD), the ON direction-selective ganglion cell (DSGC) and the transient ON-OFF cell, which is a novel type of RGC not previously described in the rabbit retina. Chapter 2 characterizes the spiking properties and synaptic inputs to the UDs, which respond to changes in the visual scene by decreasing their firing, unlike all other types of RGCs. UDs are encountered rarely and the synaptic mechanisms underlying their unusual responses have not been investigated previously. Patch-clamp recordings from UDs show that the maintained firing arises within complex spikes, which are not produced by any other type of RGC. Both ON and OFF stimuli elicit only inhibitory synaptic input, mediated largely by glycinergic amacrine cells, the immediate effect of which is to transiently suppress the maintained firing. Glycinergic inhibition also alters the properties of the complex spikes by reactivation of Na+ channels. Chapter 3 characterizes the dendritic morphology and tracer-coupling pattern of UDs filled with Neurobiotin. The UDs have a distinctive bistratified morphology, branching in stratum 1 (s1) and s4/5 of the inner plexiform layer, largely outside the cholinergic strata, with dendrites that dive retroflexively from s1 back into s4/5. UDs are tracer coupled to neighboring RGCs and are estimated to account for ~2% of the RGCs in the visual streak of the rabbit retina. UDs show tracer coupling to a type of GABAergic amacrine cell that co-stratifies with the dendrites of the UDs in s4/5. Chapter 4 examines how the synaptic inputs shape the velocity tuning of DSGCs, which comprise two main types that can be readily distinguished both morphologically and physiologically. The well characterized ON-OFF DSGCs respond to a broad range of image velocities, whereas the less common ON DSGCs are tuned to slower image velocities. The synaptic mechanisms underlying the generation of direction selectivity appear to be similar in both types in that preferred-direction image motion elicits a greater excitatory input and null-direction image motion elicits a greater inhibitory input. To examine the temporal tuning of the DSGCs, the cells were stimulated either with a grating drifted over the receptive-field center at a range of velocities or with a light spot flickered at different temporal frequencies. Whereas the excitatory and inhibitory inputs to the ON-OFF DSGCs are relatively constant over a wide range of temporal frequencies, the ON DSGCs receive less excitation and more inhibition at higher temporal frequencies. Moreover, transient inhibition precedes sustained excitation in the ON DSGCs, leading to slowly activating, sustained spike responses. Consequently, at higher temporal frequencies, weaker excitation combines with fast-rising inhibition resulting in lower spike output. Chapter 5 establishes that the ON DSGCs actually comprise two distinct types of RGCs. While both types show robust direction-selectivity, one type responds to ON stimuli with sustained firing whereas the other type responds with transient firing. The two types also have quite distinct dendritic morphologies: the sustained ON DSGCs have shorter and more numerous terminal dendrites distributed throughout the dendritic field. In addition, the transient ON DSGCs, but not the sustained ON DSGCs, show tracer coupling to a population of amacrine cells when filled with Neurobiotin. Both types have been encountered in previous studies but it was not recognized that they are distinct types. Chapter 6 characterizes a novel type of RGC that gives transient responses at light ON and light OFF and is non-directional. It can therefore be distinguished from other types of ON-OFF RGCs, including the DSGCs (which are directional) and the local-edge-detectors (which are sustained). The OFF receptive field of these ‘transient ON-OFF’ cells is narrower than the ON receptive field, whereas the converse is true for the local edge detectors. The spike responses of the cells are largely shaped by the excitatory inputs because direct inhibitory inputs are mainly recruited by stimuli that are larger than the dendritic field. Dye injection reveals that the transient ON-OFF cell has a bistratified morphology, branching between the cholinergic strata in s2 and s3/4. This type of bistratified ON-OFF RGC does not appear to have been identified in previous physiological and morphological catalogs of rabbit RGCs

Two types of ON direction-selective ganglion cells in rabbit retina

Direction-selective ganglion cells (DSGCs) respond with robust spiking to image motion in a particular direction. Previously, two main types of DSGCs have been described in rabbit retina: the ON-OFF DSGCs respond to both increases and decreases in illumination, whereas the ON DSGCs respond only to increases in illumination. In this study, we show that there are two distinct types of ON DSGCs, which can be separated by differences in their receptive-field properties, dendritic morphology and tracer-coupling pattern. While both types show robust direction-selectivity, one type responds to increases in illumination with sustained firing, whereas the other responds with relatively transient firing. The two types of ON DSGCs also have distinct dendritic morphologies: the sustained cells give rise to shorter and more numerous terminal dendrites, which are distributed throughout the dendritic field forming a space-filling lattice. In addition, the transient ON DSGCs, but not the sustained ON DSGCs, show tracer-coupling to a mosaic of amacrine cells when filled with Neurobiotin. Both types of ON DSGCs have been encountered in previous studies but were not recognized as distinct types. We propose that the two types also differ in their central projections, with only the sustained cells projecting to the medial terminal nucleus (MTN) of the accessory optic system (AOS)

Simulated Saccadic Stimuli Suppress ON-Type Direction-Selective Retinal Ganglion Cells via Glycinergic Inhibition

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

The Early-Bird Catches the Worm: An Investigative Study into the Relationship Between Sleep Behaviours and Academic Achievement

Academic achievement is paramount for students, shaping career prospects. The present study aimed to explore the factors impacting academic achievement, specifically focusing on sleep components, chronotype and perceived stress. The student sample (N = 393) consisted of 329 females (84%) 51 males (13%) and 11 non-binary individuals (3%). Participants completed an online questionnaire including measures of sleep quality, sleep hygiene, chronotype, stress and academic achievement. The data were analysed using a cross-sectional between-subjects design. Multiple regression analyses revealed that both chronotype and stress significantly predicted academic achievement. Findings suggest that high perceived stress scores, and high morningness scores are associated with high academic achievement. Sleep as a latent variable (comprising sleep quality and sleep hygiene) did not significantly predict academic achievement. These findings underscore the role of sleep behaviour and stress management in academic achievement, offering an avenue for further investigation to determine the underlying mechanisms that determine academic achievement

A novel type of complex ganglion cell in rabbit retina

The 15–20 physiological types of retinal ganglion cells (RGCs) can be grouped according to whether they fire to increased illumination in the receptive-field center (ON cells), decreased illumination (OFF cells), or both (ON-OFF cells). The diversity of RGCs has been best described in the rabbit retina, which has three types of ON-OFF RGCs with complex receptive-field properties: the ON-OFF direction-selective ganglion cells (DSGCs), the local edge detectors, and the uniformity detectors. Here we describe a novel type of bistratified ON-OFF RGC that has not been described in either physiological or morphological studies of rabbit RGCs. These cells stratify in the ON and OFF sublaminae of the inner plexiform layer, branching at about 30% and 60% depth, between the ON and OFF arbors of the bistratified DSGCs. Similar to the ON-OFF DSGCs, these cells respond with transient firing to both bright and dark spots flashed in the receptive field but, unlike the DSGCs, they show no directional preference for moving stimuli. We have termed these cells “transient ON-OFF” RGCs. Area-response measurements show that both the ON and the OFF spike responses have an antagonistic receptive-field organization, but with different spatial extents. Voltage-clamp recordings reveal transient excitatory inputs at light ON and light OFF; this excitation is strongly suppressed by surround stimulation, which also elicits direct inhibitory inputs to the cells at light ON and light OFF. Thus the receptive-field organization is mediated both within the presynaptic circuitry and by direct feed-forward inhibition

Shared and distinct retinal input to the mouse superior colliculus and dorsal lateral geniculate nucleus

The mammalian retina conveys the vast majority of information about visual stimuli to two brain regions: the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC). The degree to which retinal ganglion cells (RGCs) send similar or distinct information to the two areas remains unclear despite the important constraints that different patterns of RGC input place on downstream visual processing. To resolve this ambiguity, we injected a glycoprotein-deficient rabies virus coding for the expression of a fluorescent protein into the dLGN or SC; rabies virus labeled a smaller fraction of RGCs than lipophilic dyes such as DiI but, crucially, did not label RGC axons of passage. Approximately 80% of the RGCs infected by rabies virus injected into the dLGN were colabeled with DiI injected into the SC, suggesting that many dLGN-projecting RGCs also project to the SC. However, functional characterization of RGCs revealed that the SC receives input from several classes of RGCs that largely avoid the dLGN, in particular RGCs in which 1) sustained changes in light intensity elicit transient changes in firing rate and/or 2) a small range of stimulus sizes or temporal fluctuations in light intensity elicit robust activity. Taken together, our results illustrate several unexpected asymmetries in the information that the mouse retina conveys to two major downstream targets and suggest that differences in the output of dLGN and SC neurons reflect, at least in part, differences in the functional properties of RGCs that innervate the SC but not the dLGN