A Role for Silent Synapses in the Development of the Pathway from Layer 2/3 to 5 Pyramidal Cells in the Neocortex

Abstract

The integration of neurons within the developing cerebral cortex is a prolonged process dependent on a combination of molecular and physiological cues. To examine the latter we used laser scanning photostimulation (LSPS) of caged glutamate in conjunction with whole-cell patch-clamp electrophysiology to probe the integration of pyramidal cells in the sensorimotor regions of the mouse neocortex. In the days immediately after postnatal day 5 (P5) the origin of the LSPS-evoked AMPA receptor (AMPAR)-mediated synaptic inputs were diffuse and poorly defined with considerable variability between cells. Over the subsequent week this coalesced and shifted, primarily influenced by an increased contribution from layers 2/3 cells, which became a prominent motif of the afferent input onto layer 5 pyramidal cells regardless of cortical region. To further investigate this particular emergent translaminar connection, we alternated our mapping protocol between two holding potentials (Ϫ70 and ϩ40 mV) allowing us to detect exclusively NMDA receptor (NMDAR)-mediated inputs. This revealed distal MK-801-sensitive synaptic inputs that predict the formation of the mature, canonical layer 2/3 to 5 pathway. However, these were a transient feature and had been almost entirely converted to AMPAR synapses at a later age (P16). To examine the role of activity in the recruitment of early NMDAR synapses, we evoked brief periods (20 min) of rhythmic bursting. Short intense periods of activity could cause a prolonged augmentation of the total input onto pyramidal cells up until P12; a time point when the canonical circuit has been instated and synaptic integration shifts to a more consolidatory phase.

Postsynaptic FMRP Promotes the Pruning of Cell-to-Cell Connections among Pyramidal Neurons in the L5A Neocortical Network

“…Consistent with previous studies documenting the disappearance of silent synapses during cortical development (Rumpel et al, 2004;Harlow et al, 2010;Anastasiades and Butt, 2012), silent connection frequency was practically 0 after P19 in both postsynaptic WT and KO neurons (WT: 0.9%, 1/106; KO: 0%, 0/104; ages P19 -P30). This means that the AMPA:KA-R connectivity frequencies at P22 and P30 depicted in Figure 2 accurately represent the "total" connectivity frequency.…”

“…These data are consistent with the pruning of connections during normal maturation, when groups of synapses, based on their participation in a single cell-to-cell connection, are pruned together. Moreover, this establishes the P153 P30 time window as a pruning period that most likely includes its beginning because cortical development up to P15 is known to be a period of abundant synaptic and connection formation (Anastasiades and Butt, 2012).…”

Transient developmental increase of prefrontal activity alters network maturation and causes cognitive dysfunction in adult mice

“…The presence of neuronal ensembles capable of generating fast oscillatory rhythms during early development raises the question of whether this pattern of activity solely reflects or directly contributes to the maturation of cortical circuits and their functions. Abundant literature documented the role of coordinated electrical activity for dendrite formation, synaptic pruning and apoptosis 20-22 . To elucidate the role of neonatal fast oscillatory activity for prefrontal network maturation, we established here an optogenetic protocol for chronic early stimulation (ES) of L2/3 pyramidal neurons at the age when fast oscillations start to occur in the mPFC (Fig.…”

Questioning the role of sparse coding in the brain

“…x TINS-1151; No. of Pages 11 synapses be such a widespread phenomenon in both the neocortex and the cerebellar cortex [18,23,38,39]? The discussion of the desired level of model complexity offers an interesting possible explanation for the presence of silent synapses.…”