Circuit plasticity during up-states in mouse barrel cortex

Sleep is characterized by the cyclic occurrence of rapid eye movement (REM) sleep and non-REM sleep, which includes slow wave sleep (SWS, stages 3 and 4) and lighter sleep stages 1 and 2. In humans, the first part of the night (early sleep) consists of SWS, whereas REM sleep prevails during the second half (late sleep). In a whole network event, sleep suppresses the molecular signals that mediate LTP-related synaptic remodelling but enhances LTD-related signalling, and this effect seems to be mediated by SWS[4]. Slow oscillations have previously been observed in different cortical areas as spontaneously occurring upand down-states both in vivo and in vitro. Spontaneous upstates occur intrinsically within the cortex [5, 6]. They can also be observed in vivo in response to sensory input[7] and can be turned on and off by synaptic stimulation in vitro [8]. Memory consolidation can produce several associations and qualitative changes in memory representations, whereas sleep has the potential to outcome stabilizing effects and improve their performance, being observed in declarative and procedural memory tasks[9]. The synaptic homeostasis hypothesis proposes that the net build-up of synaptic weights, due to encoding of information during waking, is compensated during subsequent SWS. According to this hypothesis, SWS serves to globally downscale synaptic weights across the cortex, thus increasing the signal-to-noise ratio for reactivated memories and preserving the capacity of cortical networks to store new information by preventing their saturation[10]. Endocannabinoids (ECs) are a class of neurotransmitters synthesized and released from the post-synaptic membrane of cortical PNs during periods of enhanced cellular activity such as during up-states. In the cortex, activation of CB1 decreases release of 3 _____________________________________________________________________________ both GABA and glutamate[11] suggesting this local neuromodulatory system may tune network activity by regulating both excitatory and inhibitory neurotransmission within local cortical circuits. Para investigar qual dos dois processos de plasticidade neuronal (LTP ou LTD) ocorre durante a plasticidade sinaptica das redes neuronais presentes no “barrel cortex”, presente na fase de SWS, os nossos resultados indicam que apos uma experiencia protocolo de “pairing” em up-states, sao observados efeitos de LTD dada a reducao significativa dos niveis de slope e forca neuronal (EPSPs) enfraquecida. Given the importance of memory consolidations during SWS, we investigate the modulatory effects of CB1 receptors while being blocked by the antagonist AM251. The presence AM251 in a mouse barrel cortex slice resulted in an up-state amplitude decrease therefore agreeing with the importance of endocannabinoids in the modulation of SWS oscillations. To investigate which of the two processes of neural plasticity (LTP or LTD) occur during synaptic plasticity in the barrel cortex circuitry, present in SWS, our results indicate that after conducting a pairing protocol experiment in up-states, it is observed LTD effects duo to a significant reduction of slope levels and weakening neural strength (EPSPs). In sum, it is remarkable to mention that targeting the endocannabinoid system may aid in the treatment of disorder associated with impaired extinction-like processes, such as post-traumatic stress disorder. Overall these findings allow to suggest the importance of LTD during SWS in mouse barrel cortex and future projects can now proceed to in vivo experiments, in order to reveal further promising information about the underlying mechanisms of up-states in mammals and potentially enhance/inhibit the memory consolidation processing. 4 _____________________________________________________________________________