Excitation–inhibition balance in the CA3 network – neuronal specificity and activity-dependent plasticity


  • Mario Treviño,

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    • Present address: Max-Planck Institute for Medical Research Heidelberg 69120, Germany.

  • Carmen Vivar,

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    • Present address: NIH, National Institute on Aging, Biomedical Research Center, Laboratory of Neuroscience, Baltimore, MD, 21224, USA.

  • Rafael Gutiérrez

    1. Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional Apartado Postal 14-740, México D.F. 07000, Mexico
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Dr R. Gutiérrez, as above.
E-mail: grafael@fisio.cinvestav.mx


Activation of the axons of the granule cells, the mossy fibers, excites pyramidal cells and interneurons in the CA3 area, which, in turn, inhibit pyramidal cells. The integration of the various inputs that converge onto CA3 cells has been studied by pharmacological dissection of either the excitatory or inhibitory components. This strategy has the disadvantage of partially isolating the recorded cell from the network, ignoring the sources and the impact of concurrent inputs. To overcome this limitation, we dissociated excitatory and inhibitory synaptic conductances by mathematical extraction techniques, and analysed the dynamics of the integration of excitatory and inhibitory inputs in pyramidal cells and stratum lucidum interneurons (Sl-Ints) of CA3. We have uncovered a shunting mechanism that decreases the responsiveness of CA3 output cells to mossy fiber input after a period of enhanced excitability. The activation of the dentate gyrus (DG) after applying a kindling-like protocol in vitro, or after producing one or several seizures in vivo, results in a graded and reversible increase of inhibitory conductances in pyramidal cells, while in Sl-Ints, an increase of excitatory conductances occurs. Thus, interneurons reach more depolarized membrane potentials on DG activation yielding a high excitatory postsynaptic potential–spike coupling, while the contrary occurs in pyramidal cells. This effective activation of feedforward inhibition is synergized by the emergence of direct DG-mediated inhibition on pyramidal cells. These factors force the synaptic conductance to peak at a potential value close to resting membrane potential, thus producing shunt inhibition and decreasing the responsiveness of CA3 output cells to mossy fiber input.