Visual experience is necessary for maintenance but not refinement of receptive fields in

the superior colliculus

Refinement of RFs is a necessary process that occurs during maturation of sensory systems. In the visual system, refinement of receptive fields results in higher visual acuity (Prusky et al., 2004). Our results show that visual experience is necessary for the maintenance of refinement in adulthood but not for the development of refined RFs (Carrasco et al., 2005). This conclusion derives from our finding that RFs of SC neurons become refined in DR hamsters at the same rate and age as in light/dark reared hamsters, but they lose refinement and thus enlarge if the animals remain in the dark. Unexpectedly, this loss of refinement occurs around P90, when hamsters are sexually mature and considered adults. Although a previous study showed that neuronal activity is necessary for maintenance of neuronal properties (Chapman, 2000), our results were unexpected because the loss of RF refinement occurred in animals that were further into adulthood and after RFs had attained their normal size.

a) Adult plasticity in sensory systems

While the notion of brain plasticity in sensory systems has been studied primarily in juvenile systems, several studies argue that the adult and aging brain are also susceptible to modifications in response to experience or damage, although in a more limited fashion (see Chen et al., 2002; and Mahncke et al., 2006 for reviews). A very well known example occurs in the somatosensory system. Whisker trimming in adult rats leads to alterations in inhibition in the barrel cortex (Akhtar and Land, 1991; Fuchs and Salazar, 1998). That brain plasticity can occur in adults has also been shown in the auditory and visual systems. Adult barn owls can shift their midbrain sound localization map in response to distortion of visual cues by prism-rearing if they have had previous prism experience as juveniles (Linkenhoker and Knudsen, 2002). In the deep layers of the SC of guinea pigs, the auditory map is disrupted after a period of dark-rearing in adulthood (Withington et al., 1994). Thus, brain plasticity in sensory systems is not limited to the juvenile brain.

Additional examples of adult brain plasticity have been reported in the visual system. In the visual cortex of adult rodents, ocular dominance can be shifted beyond the previously defined juvenile ‘critical period’ (Guire et al., 1999; Sawtell et al., 2003; Liao et al., 2004; Pham et al., 2004). Plasticity of the visual cortex occurs in adult cats within a few hours of retinal lesion (Chino et al., 1992). Interestingly, reorganization of cortical receptive fields only occurs if the intact eye is removed, suggesting that the intact eye would compete on an activity-dependent basis with the lesioned eye. Another example of adult visual system plasticity comes from a study on adult humans that have attained a substantial improvement of visual acuity with their amblyopic eyes after practicing a visual acuity task (Levi and Polat, 1996). Although there are no examples of adult plasticity in subcortical visual structures, one anatomical study showed that

lesions to visual cortex in adult cats produce synaptic rearrangements of the retinal afferents in the LGN (Kalil and Behan, 1987). Ours is the first report of plasticity in the adult superficial SC, therefore offering novel insight into the effects of sensory experience later in life on a subcortical visual structure.

b) The role of neuronal activity in maintaining receptive field properties in the visual

system

Although numerous studies showed the importance of neural activity in the development and plasticity of neural connections and neuronal properties in the visual system, few studies have addressed their maintenance. In ferrets, blockade of glutamatergic activity in the retinae after segregation of eye-specific laminae in the LGN and before eye-opening produces

desegregation (Chapman, 2000). In visual cortex, in addition to studies suggesting that visual experience is necessary for development of direction and orientation selectivity (Mower et al., 1981; Fagiolini et al., 1994), some earlier studies suggested that it is also necessary for their maintenance. Recordings from cat visual cortex have shown that direction and orientation selectivity are recognizable as soon as visual responses can be obtained in both light and dark- reared animals, but visual experience is necessary for their maintenance after the first few weeks of postnatal life (Buisseret and Imbert, 1975, 1976; Fregnac and Imbert, 1978). Similarly, our study showed that visual experience has a stabilizing effect on RF size in the SC. Furthermore, dark-rearing after RFs are refined does not affect RF size. Spontaneous activity might have a preponderant role relatively early in life, but later, when levels of spontaneous activity decrease (Itaya et al., 1995), visual experience becomes necessary to maintain the circuitry. Our data suggest that certain levels of neuronal activity are necessary even in adulthood to preserve

neuronal properties in the SC, although we do not know whether the pattern or the amount of activity is the relevant factor in maintaining the SC circuitry (see Crair, 1999; and Chalupa, 2007 for reviews).

c) Spontaneous and visually-evoked activity during map formation

We show, as reported previously (Thornton et al., 1996), that development of gross map topography in the SC is independent of visual experience. Gross retinotopy was present at the earliest age recorded in both DR and normal animals. Several studies on non-mammalian vertebrates suggest that initial establishment of an organized representation of the visual field in the optic tectum, the non- mammalian homologue of the SC, depends on molecular cues (see Flanagan, 2006 for review) but spontaneous, correlated retinal activity is required for refinement. Spontaneous waves of correlated activity that depend first on acetylcholine and later on

glutamate have been described in the retinae of different vertebrate groups during the first postnatal weeks (Galli and Maffei, 1988; Meister et al., 1991; see Wong, 1999 for review). Studies on the role of spontaneous correlated retinal activity on the retinothalamic projection show that topography in the LGN is disrupted in mice lacking the β2 acetylcholine receptor subunit (Feller, 2002; Grubb et al., 2003; but see Sun et al., 2008). Other studies on the role of glutamatergic waves of activity point out the importance of NMDARs as coincidence detectors during map refinement. NMDAR blockade in the SC during the first two postnatal weeks disrupts the anatomical and physiological refinement of RGC axon arbors (Simon et al., 1992; Huang and Pallas, 2001) presumably by interfering with the detection of the spontaneous correlated activity that takes place in the retina during that period. In our study, we did not disrupt spontaneous activity and thus as expected map formation proceeded normally. The

relative roles of acetylcholine and glutamate-dependent spontaneous activity in the retina on the development of the retinocollicular projection remain undefined.

2. Early visual experience prevents but cannot reverse deprivation-induced loss of