Whole-Cell Patch Clamp Investigations on Rapid Synaptic Scaling of Mouse CA1 Pyramidal Neurons under Optogenetic Stimulation

Abstract: The brain consists of billions of neurons forming intricate contiguous networks. The connective strength in these networks change throughout life in response to experience and environmental stimuli. Indeed, by using these plastic mechanisms You have successfully molded networks in your brain to perform the task of reading and understanding this text. This feat is made more remarkable when considering that learning these things did not come at the expense of network stability. However, not all experiences are the same and some, such as flashing lights, can in fact cause sickness. Healthy brains are achieved and maintained by homeostatic plasticity, a set of physiological mechanisms that stabilize network activity. Synaptic scaling is one such mechanism that up- or down-regulates the firing-rates of individual neurons by changing the number of postsynaptic glutamate receptors in a cell-autonomous fashion. Synaptic scaling is thought to occur over hours, yet in order for homeostatic plasticity to work it must match the speed at which destabilizing forms of plasticity accumulate. The speed at which this happens is currently unknown for any cell, and it is therefore interesting to see if synaptic scaling happens more quickly in response to pathologies of network instability such as epilepsy. To investigate this, we measured changes in mean amplitude and interevent intervals of spontaneous excitatory postsynaptic currents in CA1 pyramidal neurons from acute hippocampal slices of CAMKIICre-ChR2 mice. This was done before, during and after optogenetic stimulation intended to model epileptic seizures using whole-cell patch clamping. The gathered results suggest that no presynaptic modulation occurs in response to the stimulation but were inconclusive on changes to postsynaptic function. Going forward, a different experimental setup is required in order to rule out the existence of rapid synaptic scaling as a natural anticonvulsive mechanism in epilepsy.