* indicates significant difference (p<0.05) from control on that day.

(C) Average spike rate per electrode in hertz from control (black) and Tsc1 KO (red) cultures across days in vitro (DIV). Bottom, example spiking data from one electrode on days 5 and 14 demonstrating a bursting pattern in Tsc1 KO cultures at DIV 14 scale bar = 5 seconds. Neurons on the bottom array (electrodes #33–64) were treated with GFP-IRES-Cre lentivirus (Tsc1 KO, red). Neurons plated on the top array (electrodes #1–32) were treated at 2 DIV with a GFP lentivirus (Control, black). Each line represents a single spike detected in a given channel during 20 seconds of a recording. Figure adapted from (B) Example raster plots of multi-unit activity recorded from Tsc1 fl/fl hippocampal neurons plated on a dual chamber probe recorded on days 5 and 14 in vitro (DIV). The dotted circles indicate the approximate plating area (~19 mm 2) over the planar electrode arrays, 150 × 150 μm inter-electrode distance.

(A) Image of a MED64 dual probe with 32 electrodes per chamber. These findings identify the TSC-mTOR pathway as a regulator of neural network activity and have implications for the neurological dysfunction in disorders exhibiting deregulated mTOR signaling.Ĭopyright © 2013 Elsevier Inc. In Tsc1 KO neurons, weakened inhibition caused by deregulated mTOR alters the balance of excitatory and inhibitory synaptic transmission, leading to hippocampal hyperexcitability. We find that the TSC-mTOR pathway is a central component of a positive feedback loop that promotes network activity by repressing inhibitory synapses onto excitatory neurons. Here, we examine the function of the tuberous sclerosis complex (TSC)-mTOR signaling pathway, a common target of mutations associated with epilepsy and autism spectrum disorder, in regulating activity-dependent processes in the mouse hippocampus. Defects in the ability to establish and maintain network homeostasis may be central to the pathogenesis of neurodevelopmental disorders.

Neural circuits are regulated by activity-dependent feedback systems that tightly control network excitability and which are thought to be crucial for proper brain development.

Karl johnson tor johnson