The neocortical microcircuit as a tabula rasa

Abstract

The neocortex has a high capacity for plasticity. To understand the full scope of this capacity, it is essential to know how neurons choose particular partners to form synaptic connections. By using multineuron whole-cell recordings and confocal microscopy we found that axons of layer V neocortical pyramidal neurons do not preferentially project toward the dendrites of particular neighboring pyramidal neurons; instead, axons promiscuously touch all neighboring dendrites without any bias. Functional synaptic coupling of a small fraction of these neurons is, however, correlated with the existence of synaptic boutons at existing touch sites. These data provide the first direct experimental evidence for a tabula rasa-like structural matrix between neocortical pyramidal neurons and suggests that pre-and postsynaptic interactions shape the conversion between touches and synapses to form specific functional microcircuits. These data also indicate that the local neocortical microcircuit has the potential to be differently rewired without the need for remodeling axonal or dendritic arbors.connectivity ͉ neocortex ͉ spines A hallmark of the neocortex is its sensitivity to environmental conditions that can drive profound structural and functional changes (1-4). At the microcircuit level, these changes include the creation, elimination, and modification of synaptic connections between neurons (5-10). To understand the mechanisms and full potential of cortical plasticity, it is essential to answer a fundamental question: How does a neuron choose to connect to only a small fraction of its neighboring neurons in a cortical volume packed with intertwined dendrites? This question has been debated extensively for more than a decade (11)(12)(13)(14)(15). At the heart of the debate is the question of whether recurrent synapses between pyramidal neurons, which are the vast majority of neocortical synapses (14, 16), are placed randomly to form an arbitrary functional microcircuit or deterministically to form a highly specific functional microcircuit.Theoretical work suggests that it is essentially impossible for an axon of a pyramidal neuron to avoid touching any other pyramidal neuron within the local microcircuit (up to Ϸ150 m from the soma) (see Fig. 1C) (14,17,18). However, experimental studies with paired recordings clearly indicate that pyramidal neurons are synaptically connected to only a small fraction of their neighboring neurons (19)(20)(21)(22)(23)(24). Even more puzzling is that when a functional connection is established, multiple synaptic contacts are observed (22,23,25,26). Furthermore, there are only enough synaptic boutons on a local pyramidal axon (Ϸ1,000-1,500) to form multiple synaptic contacts with a small fraction of the 1,000-2,000 neighboring pyramidal neurons (14,27). A form of target neuron selection must therefore take place at some level. To resolve this question, we undertook a combined multineuron recording and confocal study to compare structural and functional properties of connections between neocort...

Spontaneous and evoked synaptic rewiring in the neonatal neocortex

“…We did attempt to carry out these experiments in adult slices, but these slices do not survive such long-lasting experiments in our experimental conditions. However, it is worth pointing out that, at this age, the axonal and dendritic arborizations have already elaborated to such an extent that all axons are able to be in close apposition with all dendrites multiple times (4,5), which is most likely the essential substrate for microcircuit plasticity. In other words, a major component of microcircuit plasticity requires that the microcircuit has reached a minimal level of axonal and dendritic arborization.…”

“…Recent studies made an important step toward understanding target selection by showing that the axon of a pyramidal neuron approaches, at a submicrometer distance, the dendrites of every neighboring pyramidal neuron multiple times without any structural bias toward those with which synaptic connections are formed (4)(5)(6). This finding raised the possibility that the microcircuit could be in an all-to-all ''readiness'' to switch rapidly on and off connections between neurons in a form of rewiring plasticity without the axon or the dendrite growing toward a new target.…”

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“…In the present study, we fixed p I and p c so as to account for the neural circuitry of a typical neocortical column. Hence, we used p I = 0.25 [30] and p c = 0.15 [33,29].…”

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