Decreased expression of Tsc1 or Tsc2 has drastic impacts on synaptic function as well, but the findings vary between in vivo and in vitro experiments, suggesting non-cell-autonomous and network effects. Organotypically cultured hippocampal neurons lacking Tsc1 have higher amplitudes in mEPSCs and increased AMPA/NMDA current ratios (Tavazoie et al., 2005). However, loss of Tsc1 in hippocampal CA1 neurons in vivo impairs mGluR-dependent LTD, decreases the inter-event-interval (a measure of frequency) in mEPSCs without changing mEPSC amplitude, and increases evoked AMPA and NMDA currents proportionally (Bateup et al., 2011). Mice haploinsufficient for Tsc2 also have impaired mGluR-dependent LTD (Auerbach et al., 2011). Additionally, knockout of Tsc1 in primary hippocampal cultures has no effect on mEPSC amplitude in glutamatergic neurons, but whole cell voltage clamp analysis of GABAergic neurons shows a decrease in evoked IPSC (eIPSC) and mIPSC amplitudes (Weston et al., 2014).
