Differential involvement of β3 integrin in pre- and postsynaptic forms of adaptation to chronic activity deprivation

Neuronal networks can adapt to global changes in activity levels through compensatory modifications in pre- and postsynaptic parameters ofsynaptic transmission. These forms ofsynaptic 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 ofdissociated neurons, a preparation that lacks the specificity ofin vivo circuitry. Here, we show that there are critical differences in the properties ofsynaptic homeo- stasis between dissociated neuronal cultures and organotypic slices, a preparation that preserves more precisely in vivo connec- tivity. Moreover, the cell adhesion moleculeb3 integrin, which regulates excitatory synaptic strength, is specifically required for a postsynaptic form ofsynaptic homeostasis called synaptic scaling in both dissociated cultures and organotypic slices. Conversely, another form ofsynaptic homeostasis that involves changes in presynaptic quantal content occurs independently ofb3 integrin. Our findings define the differential involvement ofb3 integrin in two forms of synaptic homeostasis.