Physiological roles of spine motility: development, plasticity and disorders

The vast majority of excitatory connections in the hippocampus are made on dendritic spines. Both dendritic spines and molecules within the membrane are able to move, but the physiological role of these movements is unclear. In the developing brain, spines show highly dynamic behaviour thought to facilitate new synaptic connections. Dynamic movements also occur in adults but the role of this movement is unclear. We have studied the effects of the most important excitatory neurotransmitter, glutamate, and found receptor activation to enhance movement of molecules within the spine membrane. This action of glutamate may be important in regulating the trafficking of neurotransmitter receptors that mediate change in synaptic function. In addition, we have studied the dynamic interactions between pre- and postsynaptic structures labelled with FM 4-64 and a membrane-targeted GFP (green fluorescent protein), respectively, in hippocampal slice cultures under conditions of increased activity, such as epilepsy. Our findings suggest a novel form of activity-dependent synaptic plasticity where spontaneous glutamate release is sufficient to trigger changes in the hippocampal microcircuitry by attracting neighbouring spines responsive to an enhanced level of extracellular glutamate.