Target-cell-specific facilitation and depression in neocortical circuits

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In neocortical circuits, repetitively active neurons evoke unitary postsynaptic potentials (PSPs) whose peak amplitudes either increase (facilitate) or decrease (depress) progressively. To examine the basis for these different synaptic responses, we made simultaneous recordings from three classes of neurons in cortical layer 2/3. We induced repetitive action potentials in pyramidal cells and recorded the evoked unitary excitatory (E)PSPs in two classes of GABAergic neurons. We observed facilitation of EPSPs in bitufted GABAergic interneurons, many of which expressed somatostatin immunoreactivity. EPSPs recorded from multipolar interneurons, however, showed depression. Some of these neurons were immunopositive for parvalbumin. Unitary inhibitory (I)PSPs evoked by repetitive stimulation of a bitufted neuron also showed a less pronounced but significant difference between the two target neurons. Facilitation and depression involve presynaptic mechanisms, and because a single neuron can express both behaviors simultaneously, we infer that local differences in the molecular structure of presynaptic nerve terminals are induced by retrograde signals from different classes of target neurons. Because bitufted and multipolar neurons both formed reciprocal inhibitory connections with pyramidal cells, the results imply that the balance of activation between two recurrent inhibitory pathways in the neocortex depends on the frequency of action potentials in pyramidal cells.

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Figure 1: Selection of three classes of neurons in layer 2/3.
Figure 2: Anatomical and immunocytochemical identification of layer 2/3 neurons.
Figure 3: Frequency-dependent, short-term modification of glutamatergic excitatory postsynaptic potentials evoked in two classes of neurons.
Figure 4: Frequency-dependent short-term modification of GABAergic inhibitory postsynaptic potentials in two classes of interneurons.
Figure 6: Reciprocal excitatory and inhibitory connections between pyramidal and nonpyramidal cells.
Figure 5: Release mechanisms in presynaptic terminals underlie frequency-dependent short-term modification.


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We thank E. Neher, B. Katz and G. Borst for their comments on the manuscript and B. Katz for suggesting the term 'local release fraction' of vesicles. We also thank J. C. Brown, at the MRC of Canada Group on Regulatory Peptides, Vancouver, for the gift of monoclonal antibodies to somatostatin, Z. Nusser and J. D. B. Roberts for assistance with digital micrography and Z. Ahmad for excellent technical assistance.

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Correspondence to R. Lujan.

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