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Do ensembles form by excitability, not just synapses?

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Coactivating mouse L2/3 pyramids raised correlated firing with only small biphasic synaptic changes but large, persistent increases in intrinsic excitability.

Source

Intrinsic excitability mechanisms of neuronal ensemble formation

Alejandre-García T, Kim S, Pérez-Ortega J, et al. · eLife · 2022

doi.org/10.7554/elife.77470Read the full paper ↗56 citationscc by

What they did

Replicated an in vivo optogenetic imprinting protocol in mouse visual-cortex slices, coactivating L2/3 pyramids and measuring pair correlations, EPSPs, membrane resistance, and spike threshold with whole-cell and perforated patch recordings.

What they found

Coactivated cells increased correlated activity. Presynaptic plasticity was small and biphasic (depression then potentiation). Spontaneous EPSP frequency/amplitude rose even after single-cell stimulation. Strong lasting excitability gains (higher Rm, lower threshold) appeared and reversed when membrane-resistance changes were blocked pharmacologically—supporting an ‘iceberg’ model where subthreshold connections become suprathreshold.

The limits

What it doesn't show

Slice coactivation may not fully recapitulate in vivo ensemble learning; human cortical ensembles and long-term behavior were not tested.

Key terms

Neuronal ensemble
Coactive group of cortical neurons linked to perception/behavior.
Intrinsic excitability
How readily a neuron spikes given its membrane properties.
Iceberg model
Raised excitability lifts existing subthreshold synapses into functional drive.
Biphasic plasticity
Initial synaptic depression then later potentiation after recovery.
Perforated patch
Recording mode that better preserves intracellular milieu than whole-cell dialysis.

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Primary experimental tissue:

Common questions

What cells were stimulated?

Layer 2/3 pyramids in mouse visual cortex (both sexes).

Ensemble hallmark observed?

Increased correlated activity after coactivation.

Main intrinsic changes?

Higher membrane resistance and lower spike threshold.

What is the iceberg model?

Excitability makes weak existing connections effectively suprathreshold.