The process that triggers the formation of a synapse in a particular site of the large contact surface between two cells remains largely unknown. It is well known that the number of synapses that a cell is able to form is closely related to its size, however the number of synapses in a given brain region is known to change during the postnatal development reflecting what is considered a maturation process and also during the adult life which is considered an activity-dependent effect. Synapse number is a dynamic feature of all nervous systems that can be modified in the time scale of hours. The question, however, is: does the number of synapses result from a specific molecular mechanism, or is it just an epiphenomenon? In either case, does it have a limit or could it be increased or lowered freely? Would a brain modify the behaviour of the organism if the number of synapses changes only in small subset of cells or, by contrast, changes in several regions would be needed?

Brains need to maintain the appropriate number of synapses for normal cognition. Synaptic loss is the best neurobiological correlate of the cognitive deficits in Alzheimer, schizophrenia and mood disorders. However, excitatory, but not inhibitory, synapses seem to decrease in the prefrontal cortex of aged monkeys. These and other data suggest that synapse loss may be region and, even, neuronal type specific. In this context, modulation of the number of synapses in selected brain regions could be an efficient strategy to ameliorate the cognitive decline associated to normal aging or neurological pathologies.

We study the signalling pathway for synaptogenesis and the behavioural effects of changes in the number of synapses using Drosophila as experimental system. The choice of organism is justified because genetic manipulations can be elicited in selected neurons at the desired time in development, and quantitative behavioural assays can be performed on large numbers of individuals. The olfactory perception is our favoured sensory system. Current projects include:

A. FERRUS
Scientific Lab
(Cajal Institute CSIC)

1. Molecular signalling pathways for synaptogenesis.- Our group discovered the PI3K-dependent synaptogenic pathway, its conservation in human cells and its potential use to rejuvenate aged neurons (see Research Highlights). We now aim to identify other molecular components of this pathway, the effects on the postsynaptic side, and their use as genetic tools to delay neurodegeneration.
   
   
2. Olfactory perception and number of synapses.- We aim to establish a quantitative relationship between number of synapses (inhibitory and excitatory) and the olfactory index to specific odorants. In the same context, we study the neuronal substrate for the establishment of odorant habituation.
   
   
3. Ecdysone-dependent mechanisms for neuroprotection.- Ecdysone is an estrogen-like protein that plays a key role in insect physiology. We investigate the processing by which its receptor controls the transcription of target genes and, ultimately, its cellular effects including neuroprotection against ataxin.