An early critical period for long-term plasticity and structural modification of sensory synapses in olfactory cortex

Abstract

Critical periods for plasticity of thalamic sensory inputs play an important role in developing neocortical circuits. During an early postnatal time window, pyramidal cells of visual, auditory, and somatosensory cortex undergo structural refinement and possess an enhanced ability for activity-dependent synaptic plasticity. In olfactory cortex, however, pyramidal cells receive direct sensory input from the olfactory bulb, and it is unclear whether the development of olfactory sensory circuits is governed by a critical period. Here, we show that NMDA receptor-dependent long-term potentiation and dendritic spine maturation occur only during a brief postnatal time window at sensory synapses of olfactory cortex pyramidal cells. In contrast, associational synapses onto the same cells retain the capacity for plasticity into adulthood.

Figure 1.

NMDAR-dependent LTP of sensory and ASSN synapses in olfactory cortex. A, Synaptic plasticity of LOT synapses in P5–P10 rats. A₁, Recording configuration. A₂, Pairing stimulation of one LOT pathway with depolarization induces LTP (filled circles), whereas the unpaired pathway (open circles) is unaffected. Traces show EPSCs from one cell before and 30 min after LTP induction at paired (left) and control (right) inputs. A₃, APV prevents the induction of LTP at LOT synapses (open circles), whereas interleaved control recordings (filled circles) show robust LTP. A₄, LTP of LOT synapses in A₂ and A₃ does not alter the paired-pulse ratio (n = 11). Traces before and 30 min after LTP induction from one cell are superimposed (left) and scaled (right). B, Synaptic plasticity of LOT and ASSN synapses in P15–P19 rats. B₁, Recording configuration. B₂, Pairing both LOT and ASSN inputs elicits robust LTP at ASSN synapses (open circles) and weak LTP at LOT synapses (filled circles). B₃, APV blocks LTP induction at ASSN synapses. B₄, LTP of ASSN synapses in B₂ is not accompanied by a persistent change in the paired-pulse ratio (n = 5). Calibration: 5 ms, 100 pA. Rec, Recording; Pre, before; Post, after.

Figure 2.

Summary data of the magnitude of LTP at LOT and ASSN synapses during the first postnatal month (n = 3–7 slices per point). The average LOT LTP magnitudes for age groups P5–P10, P11–P14, P15–P19, P20–P26, and P30–P35 were 78 ± 11, 45 ± 17, 26 ± 11, 17 ± 4, and 3 ± 3%, respectively. The average ASSN LTP magnitudes for age groups P11–P14, P15–P19, P20–P26, and P30–P35 were 129 ± 14, 107 ± 18, 138 ± 20, and 95 ± 12%, respectively.

Figure 3.

Developmental maturation of spine density occurs rapidly at dendrites receiving LOT input. A₁, Two-photon image of a representative pyramidal cell (P34). Dashed lines indicate boundaries from which distal apical, proximal apical, and basal dendritic spines were measured. The solid line represents pial surface. Scale bar, 20 μm. A₂, Distal apical (red), proximal apical (white), and basal dendritic (blue) regions from three cells at age P5, P12, and P34. Scale bar, 5 μm. B, Developmental time course for increases in spine density at distal apical, proximal apical, and basal dendritic compartments. Each symbol represents values averages pooled over 2 d intervals. Distal apical spine density data for the nine age groups starting from P5–P6 to P34–P35 are as follows: 21 ± 0.9, 33 ± 1.5, 35 ± 3.3, 42 ± 1.6, 41 ± 0.8, 38 ± 1.0, 46 ± 1.5, 41 ± 4.6, and 45 ± 3.1 spines/100 μm; n = ∼12 cells for each age. Basal spine density data for the nine age groups starting from P5–P6 to P34–P35 are as follows: 19 ± 1.3, 32 ± 2.7, 31 ± 1.7, 43 ± 1.7, 65 ± 1.8, 61 ± 2.3, 80 ± 4.0, 75 ± 6.6, and 76 ± 3.8 spines/100 μm; n = ∼12 cells for each age. Proximal apical spine density data for the seven age groups starting from P5–P6 to P34–P35 are as follows: 22 ± 1.9, 38 ± 2.2, 41 ± 2.7, 77 ± 3.5, 76 ± 6.3, 86 ± 8.6, and 94 ± 12.3 spines/100 μm; n = ∼5 cells for each time point. Lines are exponential fits with time constants of 3, 12, and 16 d for distal apical, basal, and proximal apical dendrites, respectively.