Visual system and ocular dominance plasticity

In vertebrates, visual information gathered by the eyes has to pass the retino-collicular or the retino-geniculate pathways in the brain until it finally gets processed in the visual cortex. The visual cortex is located in both hemispheres at the back of the brain. In detail, firstly, visual information encoded by photons reaches the retina, a very light-sensitive tissue in the eye and one part of the central nervous system (CNS). The retina absorbs light photons which are converted into electrical signals like action potentials. The multilayered retina is capable of transmitting and processing visual information due to a highly complex cellular network, consisting of special types of photoreceptor cells, so called rods and cones (Figure 1 A). The propagation of signals to bipolar and horizontal cells (Figure 1 A) is carried out by chemical synapses which release the neurotransmitter glutamate in the dark perpetually. The electrochemical signals in the retina are transferred from photoreceptors via bipolar cells to the retinal ganglion cells. This signal processing is completed by additional horizontal connections, promoting lateral inhibition through horizontal and amacrine cells which are providing ‘vertical` links between bipolar and ganglion cells (Figure 1 A). The release of neurotransmitter requires a special type of chemical synapses called the ribbon synapses (Figure 1 B-E). The ribbon synapses represent a part of the presynaptic active zone and are characterized by a specific mechanism of vesicle fusion that supports a rapid release of the neurotransmitter glutamate and therefore, signal conveyance. Characteristic features of ribbon synapses are that they are being surrounded by hundreds of synaptic vesicles (Rao- Mirotznik et al., 1995) and being located in the retina in rods as well as in cones and in bipolar cells (Sjöstrand, 1958; Kidd, 1962; Missotten, 1965; Dowling and Boycott, 1966) (Figure 1 B- E). The action potentials are subsequently transmitted along optic nerve fibers from the retina via the thalamus to the visual cortex (VC) of the brain.

Introduction

Figure 1: Scheme of the mammalian retina (Figure modified from Wässle, 2004). (A) In the mammalian retina, there are six types of different neurons: rods (1), cones (2), horizontal cells (3), bipolar cells (4), amacrine cells (5) and retinal ganglion cells (6). When light in form of photons reaches a photoreceptor cell, it sends a synaptic response to bipolar cells which in turn processes information to the retinal ganglion cells. The photoreceptors are also connected with horizontal cells and amacrine cells which modify the synaptic signal before it is transferred to the ganglion cells. Rods are mostly active in dim light conditions and intermixed with cone signals that are less sensitive and work best in bright light conditions. (B) A synaptic terminal of a cone. Four presynaptic ribbons are connected to the dendrites of bipolar cells (blue) and horizontal cells (yellow). (C) A synaptic terminal of a rod. Only one presynaptic ribbon is attached to the invaginating axons of bipolar cells (blue) and horizontal cells (yellow). (D) The axon terminal of one bipolar cell (blue) contains up to 50 presynaptic ribbons and connects to postsynaptic amacrine cells (orange) and retinal ganglion cell dendrites (purple). (E) Amplified scheme of a bipolar cell ribbon synapse (blue) with an amacrine cell (orange) and a retinal ganglion cell dendrite (purple).

The amacrine cell provides a feedback synapse onto the bipolar cell.

The signal transfer from the retina to the visual cortex is mediated by axons of the retinal ganglion cells that form the optic nerve (nervus opticus). In mice, nasal retinal fibers of the optic nerve (about 80 % of all optic nerve axons) cross to the contralateral hemisphere of the brain in the optic chiasm (chiasma opticum), whereas temporal fibers project to the ipsilateral hemisphere without crossing the optic chiasm (Figure 2) (Dräger and Olsen, 1980). As the majority of nerve axons within optic fibers are projecting to the contralateral hemisphere, the

Introduction

visual cortex of mice is dominated by input signals coming from the contralateral eye, which is commonly referred to as ‘ocular dominance’ (Figure 2). Thus, in mice, only the central 30°

to 40° of the upper part of each visual hemifield is seen by both eyes (Dräger, 1975; Wagor et al., 1980; Gordon and Stryker, 1996). The lateral geniculate nucleus (LGN) receives information directly from the ascending retinal ganglion cells via the optic tract and neurons of the LGN finally send their axons to the primary visual cortex (V1). In addition, the LGN also obtains feedback connections coming from the primary visual cortex (Cudeiro et al., 2006).

Visual stimuli originating from the right visual field activate the left part of the retina, whereas the right part of the retina receives visual information coming from the left visual field. Hence, there is some degree of binocular overlap in the visual field located frontally of the mouse.

The spatial arrangement of visual stimuli in the visual field and the resulting stimulation pattern of the retinae are preserved throughout the visual pathway. Consequently, neighboring stimuli in the visual field are also activating adjacent neurons in the V1. This preservation of the spatial arrangement of visual inputs coming from retina is referred to as retinotopy and a neuronal map of the visual field as a retinotopic map (Wagor et al, 1980;

Schuett et al., 2002).

Figure 2: Representation of the mouse visual pathway and its visual field. Left and right visual fields and their respective representations in the visual pathway of the mouse are illustrated with green and blue colors. The visual information originating from the nasal part of the retina crosses to the other hemisphere in the optic chiasm (light blue and light green for right and the left eye, respectively). Visual information from the temporal

Introduction

part of the retina propagates within the same hemisphere and does not cross at the optic chiasm (dark blue and dark green for the right and left eye, respectively). Visual information in form of photons is transferred to action potentials in the retina and reaches the lateral geniculate nucleus (LGN) where it is further relayed to the primary visual cortex (V1). While the binocular part of V1 receives input coming from both eyes, the monocular part of V1 only receives input from the contralateral eye.

The visual cortex is divided into the monocular part which exclusively gets activated by visual stimulation of the contralateral eye only and the binocular part which receives inputs by visual stimulation of both eyes (Dräger, 1975). The monocular region in V1 covers the biggest area and is located at the medial side of the brain. The binocular zone is located at the lateral side of V1 and occupies only about one third of it. The frontal part of the visual field is represented in the retina of both eyes and is therefore located in the binocular zone of V1 (Gordon and Stryker, 1996). Even though the binocular visual cortex of mice receives input signals after visual stimulation of both eyes, it exhibits stronger cortical responses to stimulation of the contralateral eye and weaker responses after ipsilateral eye stimulation (Dräger, 1975;

Mangini and Pearlman, 1980; Wagor et al., 1980; Metin et al., 1988). Consequently, the visual cortex of mice is dominated by visual inputs coming from the contralateral eye and the term

‘contralateral dominance’ is used to describe this phenomenon as mentioned before.