Layer V pyramidal neuron Dendrites sample the entire cortical column. Axons project locally, and distally to basal ganglia, brainstem, & spinal cord. - Receives local inputs (from the same cortical column) and distal inputs (other cortical areas and thalamus). From Lübke et al 1996

Excitatory connections between layer V pyramidal cells Full connectivity predicted from morphology vs. Sparse (10 %) functional connectivity Kalisman et al 2005

The solution: All-to-All Potential Connectivity Unconnected Connected 6 1 2 3 4 5 Unconnected Connected # axo-dendritic touches Bouton Touch Whole-cell recordings & Confocal connection analysis 1 2 3 # boutons

Connections between interneurons & pyramidal neurons

Summary An inhibitory feedback loop is described for layer V pyramidal cells. The loop is frequency dependent, and is more prevalent than monosynaptic excitation. It is mediated by a facilitating excitatory connection onto GABAergic inhibitory neurons. The inhibition is targeted to the dendrites of pyramidal neurons (low reversal & dendritic patch experiments). Multi-patch recordings of PCs and Interneurons revealed that the loop was mediated by dendritic-targeting Martinotti cells.