Ocular dominance as a model for brain plasticity

Since the sixties of the last century, ocular dominance (the cortical response to visual stimulation of one or the other eye) has been a powerful method to study cortical processing and plasticity in the brain. It has been examined in different mammals including monkeys (Horton and Hocking, 1997), cats (Hubel and Wiesel, 1963; Hubel and Wiesel, 1970), ferrets (Issa et al., 1999) and rats (Domenici et al., 1992; Maffei et al., 1992; Fagiolini et al., 1994).

However, presently the mouse visual cortex has become the standard model to investigate OD-plasticity because it shares both many similarities to the visual system of humans and there are versatile investigations possible due to the large number of available genetically modified knockouts (Dräger, 1978; Gordon and Stryker, 1996; Bartoletti et al., 2002; Lehmann and Löwel, 2008 Frenkel and Bear, 2004; Tagawa et al., 2005; Hofer et al., 2006) (for review see Espinosa and Stryker (2012) and Levelt and Hübener (2012)).

Introduction

Animals like carnivores and primates have a refined visual system which includes a much larger cortical region for visual processing and orientation. Unlike mice, they show orientation columns in the visual cortex, meaning that groups of neurons within a column perpendicular to the surface of the cortex have nearly identical receptive fields and similar response properties which is commonly referred to as ‘columnar organization` (Hubel et al., 1976; Issa et al., 2000; Ohki and Reid, 2007; Van Hooser, 2007; DeFelipe et al., 2012).

Still, the overall organization of the mouse visual cortex remains relatively simple which renders it an excellent model system for combining and bringing theoretical models into closer compliance with biological reality and relevance (Blais et al., 2008; Ohki et al., 2005). In rodents like rats and mice, neural cells in the visual cortex are not organized in orientation columns and therefore exhibit a lower degree of spatial organization in comparison to primates or carnivores (Ohki et al., 2005; Van Hooser, 2007). This phenomenon is referred to as ‘salt-and-pepper’ organization (Kaschube, 2014; for review see: Espinosa and Stryker, 2012). For pyramidal cells located in the surface of mouse V1, it has been reported that neurons with similar visual response properties excite each other (Harris and Mrsic-Flogel, 2013; Ko et al., 2011; Li et al., 2013; Lien and Scanziani, 2013; Wertz et al., 2015) but the anatomical basis of this synaptic network is still vastly unknown.

Contradictory to the fact that axons and dendrites of all orientation selectivity’s pass near each other with roughly equal chance; it was shown that pyramidal neurons of similar orientation selectivity are forming synapses with each other and neurons with similar orientation tuning form larger synapses (Lee et al., 2016). In addition to that it was postulated that neurons in layer 2/3 pyramidal neurons of the mouse visual cortex exhibit similar motion direction preferences, which were developing layer-specific functional modules. In most of the networks (about two thirds), the direction preference varied between the layers, whereas in about one-third of the networks, the layer modules were locked to the direction preference of the postsynaptic neuron (Wertz et al., 2016).

OD-plasticity in the visual cortex is a method to study how experience and deprivation of one eye may modify connections in the brain (Blais et al., 2008). The mammalian primary visual cortex is not fully mature at birth and not even at the time of eye opening, both anatomically and physiologically. Hence, the cortex still shows plasticity and continuously develops further during the first weeks of postnatal life (Hubel and Wiesel, 1963; Blakemore and Van Sluyters, 1975; Dobson and Teller, 1978; Fregnac and Imbert, 1978; Albus and Wolf, 1984; Boothe et

Introduction

al., 1985; Fagiolini et al., 1994). Input signals from the two eyes firstly converge in the primary visual cortex (Wiesel and Hubel, 1963), where competitive interactions of the synapses determine which eye will eventually dominate both, functionally and anatomically (Sugiyama et al., 2008). For example, juvenile mice show less visual acuity than adult mice, nevertheless they achieve adult-like visual acuity at around postnatal day 28 (Prusky et al., 2006). In the mouse visual cortex, neurons have been shown to be orientation as well as direction-selective (Dräger, 1975; Metin et al., 1988; Sohya et al., 2007; Niell and Stryker, 2008; Wang et al., 2010). Already before eye opening, retinal ganglion cells exhibit strong direction selectivity (Elstrott et al., 2008; Yonehara et al., 2009) which is not dependent on visual experience (Elstrott et al., 2008; Chen et al., 2009; Yonehara et al., 2009; Rochefort et al., 2011). However, ocular dominance and binocular vision are rudimentary in immature animals (Sherman and Spear, 1982; Fagiolini et al., 1994). The gradual development of these functional properties during subsequent postnatal periods depends critically on appropriate visual experience (Gianfranceschi et al., 2003). During this critical period early in life, visual neurons develop their adult functional properties in response to visual stimuli. Hence, an extensive anatomical reorganization of connections in the visual cortex takes place (Fagiolini et al., 1994). The ocular dominance of binocular neurons in the visual cortex is actively maintained by competition between synapses which are serving the two eyes (He et al., 2006). In the binocular part of the visual cortex, neurons respond to inputs from both eyes, but remain to be dominated by the contralateral eye as shown in rodents (Dräger, 1975, 1978). Early during the developmental phase, connections in the mammalian central nervous system proceed through a period (known as the critical period) in which they exhibit a high degree of plasticity (Wiesel and Hubel, 1963; Gordon and Stryker, 1996; Hensch, 2005). Both, anatomical and functional development, depend greatly on visual experiences during this early phase of plasticity. In the visual cortex, this critical period ends after approximately 5 years in humans, 12 weeks in kittens and around 35 days in mice (Gordon and Stryker, 1996).

After this critical point of time in development, the capacity for experience-dependent changes in the brain is substantially reduced through several mechanisms which are not fully understood yet (Sawtell et al., 2003; Schwarzkopf et al., 2007; Lehmann and Löwel, 2008;

Morishita and Hensch, 2008). It is assumed that plasticity mechanisms in the brain are

Introduction

2008; Mrsic-Flogel et al., 2007). In adult mice, it is thought to be mediated by a different mechanism that requires α-calcium/calmodulin-dependent kinase II (αCaMKII) auto phosphorylation (Ranson et al., 2012). Visual experience acts by modulating the level of neural activity within the visual pathway (Fagiolini et al., 1994). It also plays a crucial role in strengthening, remodeling and the elimination of synapses during development of the visual system (Shatz et al., 1990; Fagiolini et al., 1994). Although early studies on ocular dominance were performed with cats (Wiesel and Hubel, 1963; Hubel and Wiesel, 1970), the mouse visual cortex has now become a standard model to examine OD-plasticity (Frenkel and Bear, 2004; Tagawa et al., 2005; Hofer et al., 2006).

An extensively investigated model for neuronal plasticity in the brain is the so-called ocular dominance (OD) plasticity. This is accomplished by depriving the contralateral eye of mice of vision which can result in a change in the ocular dominance. More precisely, neurons in the binocular region of V1 change their responsiveness and get activated equally strong by stimulation of each eye (Dräger, 1975; Gordon and Stryker, 1996).