Plasticity associated with Up/Down states in the mouse barrel cortex

Slow wave sleep is characterised by synchronised slow oscillations, which manifest themselves in cortical neurons as depolarised Up states and more hyperpolarised, silent Down states. Up/Down states have been implicated in synaptic plasticity during sleep-associated memory consolidation. However, the underlying mechanism is not well-understood. I used the mouse somatosensory barrel cortex as a model system to investigate whether Up states and Down states differentially facilitate synaptic plasticity. Initial experiments were carried out in vitro in slices of barrel cortex. Here, Up states were evoked by electrical stimulation, making it possible to precisely control onset timing. Perforated patch-clamp recordings were obtained from pyramidal neurons in layer 2/3 to determine whether pairing of inputs with electrically-evoked Up states results in plasticity of the paired input. I found that pairing a train of EPSPs at different frequencies with Up states resulted in synaptic depression. However, there was no significant difference between Up states and Down states in their propensity to mediate plasticity of paired inputs. This lack of state-dependent plasticity could have been due to an insufficient number of pairings, as well as differences between electrically-evoked and spontaneous Up states in their ability to facilitate plasticity of paired inputs in the barrel cortex. To overcome these issues, plasticity was studied using long-term extracellular recordings in vivo under anaesthesia. Here, spontaneous Up states were automatically detected and paired with whisker deflections. While persistently pairing inputs with Up states led to long-term depression of the whisker response in the barrel cortex, Down state pairings did not induce any long-term effects. Taken together, results from experiments in vivo, but not in vitro, suggest that Up states facilitate depression of inputs in an activity-dependent manner.