Kurzfassung

Neuronal communication is modulated by adaptive responses to changes in the environment and to pathological brain activity. The visual system has been a model for the investigation of homeostatic regulation of neuron and network homeostasis. Thus, changes in visual experience such as visual deprivation alters synaptic function in the visual cortex. A key mechanism underlying such modulation is multiplicative up- or downscaling of synaptic strength..AMPA receptors (AMPARs) mediate most of the...
Neuronal communication is modulated by adaptive responses to changes in the environment and to pathological brain activity. The visual system has been a model for the investigation of homeostatic regulation of neuron and network homeostasis. Thus, changes in visual experience such as visual deprivation alters synaptic function in the visual cortex. A key mechanism underlying such modulation is multiplicative up- or downscaling of synaptic strength. . AMPA receptors (AMPARs) mediate most of the fast excitatory transmission in the CNS. AMPARs comprise four core subunits and several auxiliary subunits, many of which exert a strong influence on receptor function. We and others have observed that the expression of auxiliary subunits is regulated in an activity-dependent manner. Thus, epileptic activity decreases the expression of two auxiliary subunits, namely CKAMP44 and TARP g-2, in the hippocampus. Additionally, visual deprivation increases the expression of the same proteins in the cortex and thalamus of mice. Moreover, we found that auxiliary subunits are highly regulated also in the cortex of epileptic patients indicating that changes in the expression of these proteins is a general mechanism underlying homeostatic regulation of AMPAR and synapse function. We tested this hypothesis by investigating the requirement of CKAMP44 for homeostatic plasticity in the hippocampus and cortex using CKAMP44 knockout mice. CKAMP44 was indeed necessary for kainate-induced changes in synapse function in the dentate gyrus of the hippocampus and for visual-deprivation-induced changes in synapse function in the lateral geniculate nucleus (LGN).
In the next funding period, we will investigate whether and how synaptic communication and network activity changes due to homeostatic regulation of CKAMP44 expression. The main consequence of the visual-deprivation-mediated upregulation of CKAMP44 expression is a more pronounced synaptic short-term depression. We predict that this affects computation and increases transfer rates of visual information in LGN and visual cortex. We will test our hypothesis by investigating the influence of visual deprivation on responses of neurons to visual stimuli in head-fixed non-anesthetized mice. To this end, we will record neuron activity in LGN and visual cortex simultaneously using Neuropixels probes. We will quantify response amplitudes, transfer rates, and tuning curves. By correlating data from ex vivo and in vivo electrophysiology with computational modeling, we will reveal how homeostatic upregulation in CKAMP44 expression alters synapse function and thereby influences computation of neurons in the visual system.» weiterlesen» einklappen