Functional heterogeneity of human and mouse layer 5 pyramidal neurons

Moradi-Chameh, Homeira (1), Shah, Prajay (2), Tripathy, Shreejoy (3), Valiante, Taufik (4)

1: Krembil Research Institute

2: Krembil Research Institute

3: Krembil Center for Neuroscience

4: Krembil Research Institute

Background: Intrinsic biophysical diversity in excitable cells manifests as differing spike outputs to similar current inputs despite the cells being of the same molecular class. Such functional heterogeneity is advantageous since it increases the information within a population of neurons. Despite there being clear evidence for functional heterogeneity in early sensory afferents, it is unknown whether the cortex also employs heterogeneity as a fundamental organizing principle.

Methods: We performed in-vitro whole-cell recording of Layer 5 pyramidal cells from freshly excised tissue slices from patients undergoing epilepsy surgery for temporal lobe epilepsy and acute mouse brain slices. All experiments were performed with synaptic blockers. We recorded principle cell responses to an identical Gaussian filtered white noise current stimulus 2.5s long (n = 7 mouse and human cells each, 30 trials/cell). The noise variance (σ) was 10% and 20% of the direct current (25–200 pA; σ =20 and 40 pA) offset for each cell.

Results: We observed lower pair-wise correlations between spike trains of different cells versus trials from the same cell. Linear decoding approaches estimate how well each cell’s spike train encodes the input stimulus. The reconstructed stimulus operated on a mean timescale of 21.5ms +/- 9.2, but showed considerable heterogeneity amongst cells.

Conclusion: These results suggest that functional heterogeneity is a property of both human and mouse cortical neurons. Such diversity may contribute to increased overall information representation within cortical circuits.