The long term goal of this research project is to elucidate the functions of neural network in the retina. A key function of the retina is to encode distinct components of the image world, such as color and motion, by multiple neural networks. Direction selective ganglion cells (DSGCs) play a major role in motion detection because they respond to an object as it moves in a particular direction. Starburst amacrine cells (SACs) contribute to direction selectivity in DSGCs by releasing GABA onto a DSGC only when an object moves from its proximal to distal dendrites, but not when an object moves in the opposite direction, resulting in unidirectional DSGC excitation. While the classic Barlow-Levick model remains the fundamental explanation of direction selectivity, this model does not explain acetylcholine release from SACs and heterologous synaptic connections between bipolar cells and SACs. Using patch clamp recordings together with morphological and molecular biological approaches, we have investigated the temporal properties of individual bipolar and ganglion cells and correlated neural circuits coding components of the image world. We recently found that type 2 and 7 bipolar cells express bungarotoxin-sensitive, ?7 acetylcholine receptors (?7AChRs) and depolarize in response to a puff application of a ?7AChR agonist. Because these bipolar cells provide synaptic inputs to SACs at their proximal dendrites, we propose a new model of direction selectivity: when an object moves from proximal to distal dendrites of SACs, the type 2 and 7 bipolar cells are activated through ?7AChR signaling and boost the excitation in SACs (preferred direction for SACs). In contrast, activation of these bipolar cells is delayed by an object moving in the opposite direction, which in turn provides less excitation to SACs (null direction for SACs). We will explore this model as follows: we will investigate the types of bipolar cells that express ?7AChRs using immunohistochemistry and patch clamp recordings (Aim 1). Then, we will generate a transgenic mouse in which ?7AChRs are eliminated from bipolar cells. Using this mouse, we will test whether the direction selectivity of SACs is reduced (Aim 2). Finally, we will test whether the direction selectivity of downstream neurons is reduced by ?7AChRs elimination from bipolar cells (Aim 3). The results of this study will increase our understanding of neural mechanisms of motion detection.
The retina is the entrance to the visual system where many kinds of neurons capture images and process them. We will examine functions and connections of retinal neural network in response to a moving object. This study will contribute to the elucidation of how retinal network play a role in visual recognition.
| Hellmer, Chase B; Clemons, Melissa Rampino; Nawy, Scott et al. (2018) A group I metabotropic glutamate receptor controls synaptic gain between rods and rod bipolar cells in the mouse retina. Physiol Rep 6:e13885 |
