a1 MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, UCL, Gower Street, WC1E 6BT London, UK
a2 Department of Neuroscience, Physiology and Pharmacology, UCL, Gower Street, WC1E 6BT, London, UK
Neuronal networks can adapt to global changes in activity levels through compensatory modifications in pre- and postsynaptic parameters of synaptic transmission. These forms of synaptic plasticity are known as synaptic homeostasis, and are thought to require specific cellular interactions and signaling across the entire neuronal network. However, the molecular mechanisms underlying synaptic homeostasis have so far been investigated mostly in primary cultures of dissociated neurons, a preparation that lacks the specificity of in vivo circuitry. Here, we show that there are critical differences in the properties of synaptic homeostasis between dissociated neuronal cultures and organotypic slices, a preparation that preserves more precisely in vivo connectivity. Moreover, the cell adhesion molecule β3 integrin, which regulates excitatory synaptic strength, is specifically required for a postsynaptic form of synaptic homeostasis called synaptic scaling in both dissociated cultures and organotypic slices. Conversely, another form of synaptic homeostasis that involves changes in presynaptic quantal content occurs independently of β3 integrin. Our findings define the differential involvement of β3 integrin in two forms of synaptic homeostasis.
c1 Correspondence should be addressed to: Lorenzo A. Cingolani or Yukiko Goda, MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, UCL, Gower Street, London WC1E 6BT, UK phone: +44 20 76793531 fax: +44 20 76797805 emails: firstname.lastname@example.org; email@example.com