Presynaptic Development at L4 to L2/3 Excitatory Synapses Follows Different Time Courses in Visual and Somatosensory Cortex

Abstract

Visual and somatosensory cortices exhibit profound experience-dependent plasticity during development and adulthood and are common model systems for probing the synaptic and molecular mechanisms of plasticity. However, comparisons between the two areas may be confounded by a lack of accurate information on their relative rates of development. In this study, we used whole-cell recording in acute brain slices to study synaptic development in mouse barrel and visual cortex. We found that short-term plasticity (STP) switched from strong depression at postnatal day (P)12 to weaker depression and facilitation in mature cortex. However, presynaptic maturation was delayed by ϳ2 weeks at layer (L)4 to L2/3 excitatory synapses in visual cortex relative to barrel cortex. This developmental delay was pathway-specific; maturation of L2/3 to L2/3 synapses occurred over similar timescales in barrel and visual cortex. The developmental increase in the paired-pulse ratio to values greater than unity was mirrored by a developmental decrease in presynaptic release probability. Therefore, L4 to L2/3 excitatory synapses had lower release probabilities and showed greater short-term facilitation in barrel cortex than in visual cortex at P28. Postsynaptic mechanisms could not account for the delayed maturation of STP in visual cortex. These findings indicate that synaptic development is delayed in the L4 to L2/3 pathway in visual cortex, and emphasize the need to take into account the changes in synaptic properties that occur during development when comparing plasticity mechanisms in different cortical areas.

Synapse-Specific Control of Experience-Dependent Plasticity by Presynaptic NMDA Receptors

“…In support of our findings, we previously found that visual deprivation can either reduce or fail to alter the PPR at L4-L2/3 synapses, the key difference being whether preNMDARs are blocked (Philpot et al, 2001; Yashiro et al, 2005). Our findings are broadly consistent with an experience-dependent reduction in presynaptic glutamate release at L4-L2/3 synapses during development, an effect that coincides with a reduction in preNMDAR function, GluN3A expression, and GluN1 labeling at excitatory presynaptic terminals (Cheetham and Fox, 2010; Corlew et al, 2007; Larsen et al, 2011). Collectively, our results suggest that sensory deprivation alters preNMDAR functions via changes confined to a restricted number of synaptic sites and that these effects are only revealed at certain activation frequencies.…”

Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1−/y mice

“…Data were filtered at 3 kHz and sampled at 20 kHz. No statistical methods were used to pre-determine sample sizes, but our sample sizes are similar to those reported in previous publications 55,56 . data analysis.…”

NR3A-containing NMDARs promote neurotransmitter release and spike timing–dependent plasticity

“…Synaptic responses evoked by L4 stimulation and recorded in L2/3 undergo a developmental shift, from paired-pulse depression in the juvenile visual cortex to paired-pulse facilitation, at a time when Nr3a is downregulated and preNMDARs are no longer tonically active (>P28) 29 . To test for a role of Nr3a in evoked transmitter release, we analyzed the paired-pulse ratio (PPR) in V1 L2/3 synapses before and after d -AP5 application in Nr3a −/− mice and their wildtype controls (P13–18).…”

“…Nr2b-containing, Nr3a-lacking preNMDARs in the mature cortex are not tonically active, but may become active in strongly depolarizing conditions, such as during high frequency bursts, which presumably remove the magnesium block. Thus, Nr2b-containing preNMDARs expressed in the mature neocortex may promote the facilitation of repetitive stimuli, which predominate in the mature visual cortex 29 .…”