FUNCTIONAL RECOVERY FOLLOWING NEURAL INJURY IN EMBRYOS

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A question important to basic and clinical neuroscience is why the developing nervous system seems more capable of functional repair after injury than the adult. A related question is whether adult neurons can recover from injury using-mechanisms successfully employed by developing neurons. Despite intense research in this area, few studies have analyzed the response of single identified neurons in developing versus adult animals with regard to anatomical, physiological and behavioral recovery of function following injury. In the leech's relatively simple nervous system it is possible to study not only behavior, its modulation and the underlying neuronal circuit, but also the effects of discrete lesions on individual connections and behavior. In addition, many neurons are identifiable early in embryogenesis, allowing investigations into the development of individual.neurons and their connections both in normal and injured embryos. This proposal is focussed on a single interneuron in the leech, the S cell, which in adult animals responds to injury in a characteristic fashion. In addition, the S cell has been shown to be essential to normal nonassociative learning of a sensory-motor reflex (shortening) even though it is not required for the reflexive behavior but only for its modification. Embryonic lesions that kill an S cell cause the formation of at least one aberrant connections that restores some normal physiological functioning. Experiments outlined in this proposal test specific hypothesis concerning the cellular mechanisms used by embryonic neurons to form atypical connections and the ability of these connections to support nonassociative learning. In addition, the stability of atypical connections formed during development can be analyzed later in adulthood. Experimental methods include anatomical, physiological and behavioral techniques in combination to characterize S cell synaptic connections, atypical connections formed following injury and their link to nonassociative learning. These experiments will provide insights into cellular mechanisms underlying the developing nervous system's compensatory response to injury and into mechanisms in embryos and adults for the recovery of complex behavior.