ZEBRAFISH PLASTICITY

Experience-dependent modifications of developing neural circuits and animal behaviours

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 Obiettivo del progetto (Objective)

'During development, neuronal connectivity is initially established by genetically determined intrinsic factors, e.g. molecular cues and spontaneous activity, generating networks according to a 'best guess' strategy. However, with the appearance of sensory organs, external inputs will refine these connections, allowing adaptation to the environment. In the Xenopus developing visual system, repetitive moving visual stimuli induce long lasting changes in the direction-sensitivity of some tectal neurons, apparently via modification of synaptic strength. However, it is still unknown how this synaptic plasticity contributes to the refinement of neural circuits for precise information processing and adjustment of animal’s behaviours. Using a multidisciplinary approach combining cutting-edge genetic engineering methods to monitor and manipulate activity of specific neurons or entire circuits, development of novel mathematical and computational methods and kinematic analyses of motor behaviours, I will investigate how sensory visual experience may affect the activity and interaction of the optic tectum neuronal circuit and motor behaviour. These experiments will contribute to our understanding of the role of sensory experience in shaping the development of neural circuits and animal behaviour. They will also shed light into the mechanisms by which the nervous system self wires, adapts, and learns. The study of these mechanisms might contribute to the design of new therapeutic treatments for developmental disorders associated with impaired nerve connections.'

Introduzione (Teaser)

Visual stimulation can shape nerve networks for adaptation to the environment. Recent research has identified mechanisms that control self-wiring, adaptation and learning in the nervous system.

Descrizione progetto (Article)

To date, most research on nervous system plasticity has used sensory stimulation and measurements of the induced neural responses. The 'Experience-dependent modifications of developing neural circuits and animal behaviours' (ZEBRAFISH PLASTICITY) project used sensory perception to better isolate neuronal activities.

Project researchers used a technique resembling the motion after-effect (MAE). A phenomenon seen in mammals and some insects, continuous coherent motion eventually induces the perception of movement in the opposite direction even after terminating the stimulus. The team opted for the small zebrafish larva to monitor large neural networks as it has conveniently transparent skin.

ZEBRAFISH PLASTICITY designed a two-photon microscope to visualise brain activity using fluorescence at a single cell level with a specially developed transgenic line of zebrafish.

Results suggest that within the optic tectum exist direction-selective neural networks that correlate with either visual detection or visual perception. Unlike the first group, the visual perception group showed synchronous activities in the absence of visual stimulation with suppressed activity during the conditioning moving stimulus. Imbalance is generated when the first group is habituated to motion perception while the second group is not, resulting in motion illusion.

Overall, motion perception requires a specific group and not all direction-selective neurons. As these are randomly distributed within the network, sensory perception seems to depend on activation of a minimum number of direction-selective neurons to induce motion perception.

Applications may extend to humans as observations in autistic patients report an enhanced MAE. Accordingly the team has generated a zebrafish with a specially modified gene linked to autism and Rett's syndrome. Future research plans for the team include tests on the new line to elucidate neural circuit anomalies that may lead to autism.