The contribution of protein kinases to plastic events in the superior colliculus

1. The superior colliculus (SC)/optic tectum is a multi-layered midbrain area that harbours representations of visual and auditory space and somatic body surface. The development and maintenance of these sensory maps has been shown to involve activity and experience-dependent mechanisms. 2. The implantation of an extra eye primordium into the developing forebrain of Rana pipens results in the formation of dually innervated tecta that would have normally be solely innervated by the contralateral retina. The retinal projections are arranged in an interdigitating pattern of alternate stripes of terminations from each retina. The establishment of this striped pattern requires retinal activity and depends on N-methyl-D-aspartate (NMDA) receptors. Manipulation of protein kinase activity leads to the formation of an abnormal stripe pattern. 3. Regeneration of the goldfish retinotectal projection, following crush of the optic nerve, occurs in an activity dependent manner involving NMDA receptors. Furthermore, a critical period exists, during which retinal activity is vital for reformation of the visual map. Protein kinase manipulations during this period disrupt normal reformation. The same manoeuvres at other time points have little effect on map reformation. 4. An unusual form of long-term potentiation (SC-LTP) has been demonstrated in the in vitro preparation of the guinea-pig SC. By stimulating the optic layer of the SC, a postsynaptic potentiation can be recorded in the superficial grey layer. The expression of SC-LTP is masked but not prevented by blockade of NMDA receptors. The role of protein kinases in this form of synaptic modification has also been studied using various manipulations and inhibitors with varying substrate specificity. Whereas H7, an inhibitor reputed to be protein kinase C specific, only masks the expression of SC-LTP, K252a which has a broad substrate specificity blocks the induction of SC-LTP. 5. Experience-dependent formation of the auditory space map in the deeper layers of the SC is believed to be under the instruction of the visual representation in the superficial layers. Furthermore, a crucial period exists during which normal auditory and visual experience are required for successful establishment of the auditory map. Chronic exposure to 5-aminophosphonopentanoic acid (AP5) during this time prevents the formation of the map. Chronic exposure to K252a, a broad kinase inhibitor, over the same time period, also disrupts the formation of the auditory space map. 6. Taken together, these models emphasise the role of protein kinases in synaptic plasticity observed in the SC. Furthermore, interference with protein kinase activity at crucial stages of regeneration or development appears to disrupt the sequence of events that lead to the consolidation of SC receptive fields.