Synaptic Activity and the Construction of Cortical Circuits

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Science  15 Nov 1996:
Vol. 274, Issue 5290, pp. 1133-1138
DOI: 10.1126/science.274.5290.1133


  • Fig. 1.

    Development of axonal arbors at different locations along the visual pathway. The terminal arbors of axons are shown at various embryonic (E) and postnatal (P) ages (in days) in cats. In all cases, the emergence of the adult pattern of connections is the result of considerable sprouting and proliferation of axon branches, accompanied by much more limited elimination of small collaterals at inappropriate locales. These morphological changes suggest that the strategy for forming adult circuits involves a local control of sprouting and synaptogenesis rather than selection from a large pre-existing repertoire [modified from (25)].

  • Fig. 2.

    Organized patterns of spontaneous activity in the developing retina and cortex. In the retina, waves of action potentials spread between cohorts of retinal ganglion cells, visualized here by calcium imaging. Each region represents a different event, and the intensity of the color indicates the direction of propagation. In the cortex, groups of neurons, indicated by the colored areas, undergo spontaneous changes in their intracellular calcium concentrations; unlike the retinal waves, these events propagate via gap junctions and do not require synaptic transmission and action potentials. Despite mechanistic differences, both phenomena produce highly correlated patterns of activity that are thought to be important in guiding circuitry formation. Scale bar, 100 μm. Left panel is from (24) and right panel is from (86).

  • Fig. 3.

    Long-term potentiation (LTP) at two different synapses in the neocortex. (A) LTP of thalamocortical connections in the rodent somatosensory system is restricted to early postnatal life. The top panel shows the recording arrangement in a slice that includes intact connections between the thalamus (VB) and primary somatosensory cortex (CTX). Pairing stimulation of VB (STIM) with depolarization of recipient cells in layer 4 (REC) of cortex in young animals (age P3 to P7) leads to robust LTP; the same protocol in older animals (age P8 to P14) does not lead to synaptic enhancement (lower panel). (B) Intrinsic connections of the visual cortex can also undergo LTP. Stimulation with theta-burst stimulation (TBS) of layer 4 (in young and old animals) leads to robust enhancement of the extracellular field potential recorded in layer 3. This form of cortical LTP is remarkably similar to LTP observed in the hippocampus. EPSP, excitatory postsynaptic potential. (A) is modified from (54) and (B) is modified from Kirkwood and Bear (52).

  • Fig. 4.

    Differences between the morphological and functional state of developing circuits in the visual cortex. In juvenile animals, intrinsic horizontal axon collaterals (top panels) extend for considerable distances (seen here in tangential view), but only form functional connections locally (red dots). Optical recordings (lower panels) of coronal slices of visual cortex similarly show that horizontal activation is restricted to a region considerably smaller than the extent of developing collaterals, implying that synapses along distal collaterals are weak or absent. In adult animals (right panels) axon terminals are found in distinct laterally placed clusters, and optical recordings with voltage-sensitive dyes demonstrate that these can supply functional connections. Wm, white matter. Scale bar, 1 mm. After (66).

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