Pattern-specific associative long-term potentiation induced by a sleep spindle-related spike train.
Spindles are non-rapid eye movement (non-REM) sleep EEG rhythms (7-14 Hz) that occur independently or in association with slow oscillations (0.6-0.8 Hz). Despite their proposed function in learning and memory, their role in synaptic plasticity is essentially unknown. We studied the ability of a neuronal firing pattern underlying spindles in vivo to induce synaptic plasticity in neocortical pyramidal cells in vitro. A spindle stimulation pattern (SSP) was extracted from a slow oscillation upstate that was recorded in a cat anesthetized with ketamine-xylazine, which is known to induce a sleep-like state. To mimic the recurrence of spindles grouped by the slow oscillation, the SSP was repeated every 1.5 s (0.6 Hz). Whole-cell patch-clamp recordings were obtained from layer V pyramidal cells of rat somatosensory cortex with infrared videomicroscopy, and composite EPSPs were evoked within layers II-III. Trains of EPSPs and action potentials simultaneously triggered by the SSP induced an NMDA receptor-dependent short-term potentiation (STP) and an L-type Ca2+ channel-dependent long-term potentiation (LTP). The number of spindle sequences affected the amount of STP-LTP. In contrast, spindle trains of EPSPs alone led to long-term depression. LTP was not consistently induced by a regular firing pattern, a mirrored SSP, or a randomized SSP; however, a synthetic spindle pattern consisting of repetitive spike bursts at 10 Hz reliably induced STP-LTP. Our results show that spindle-associated spike discharges are efficient in modifying excitatory neocortical synapses according to a Hebbian rule. This is in support of a role for sleep spindles in memory consolidation.
Rosanova
Mario
M
Department of Physiology, University of Bern, 3012 Bern, Switzerland.
Ulrich
Daniel
D
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002415:Cats; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012890:Sleep / Q000502:physiology*; D013003:Somatosensory Cortex / Q000502:physiology*