Aim: 

Cysteine string protein-alpha (CSP-alpha) is a synaptic vesicle protein related to Hsp40 co-chaperones that cooperates with alpha synuclein to prevent nerve terminal degeneration. Probably, CSP-alpha action is most required when continuous synaptic activity increases but detailed mechanisms are not well known.

Methods: 

We have used hippocampal cultures from control and knock-out mice lacking CSP-alpha to (i) measure postsynaptic currents using the patch-clamp technique and to (ii) study the number and the structure of synapses with inmunocytochemical and electron microscopy approaches.

Results: 

We have found that CSP-alpha is not a major player to execute excitatory neurotransmission in autaptic hippocampal cultures. In contrast, in long-term neuronal cultures forming networks of excitatory and inhibitory neurons, CSP-alpha is required to maintain synapse number. Unexpectedly, the frequency of excitatory AMPA mEPSC is normal but the amplitude progressively decreases in parallel with culture aging. Those changes resemble the typical synaptic scaling of homeostatic plasticity triggered by blockers of inhibitory synapses. Consistently, we discovered that the number of GABAergic synapses was dramatically reduced in the cultures lacking CSP-alpha. Furthermore, highly active parvalbumin-expressing interneurons almost disappeared while the number of less active calretinin-expressing interneurons was not altered.

Conclusion: 

Altogether, our results reveal a preferential need for CSP-alpha to maintain GABAergic synapses and probably highly active interneurons.

Funding: 

MICINN (BFU2007-66008) and Consejería de Innovación Ciencia y Empresa -Junta de Andalucía.