Inference of neuronal functional circuitry with spike-triggered non-negative matrix factorization

Neurons in sensory systems often pool inputs over arrays of presynaptic cells, giving rise to functional subunits inside a neuron’s receptive field. The organization of these subunits provides a signature of the neuron’s presynaptic functional connectivity and determines how the neuron integrates sensory stimuli. Here we introduce the method of spike-triggered non-negative matrix factorization for detecting the layout of subunits within a neuron’s receptive field. The method only requires the neuron’s spiking responses under finely structured sensory stimulation and is therefore applicable to large populations of simultaneously recorded neurons. Applied to recordings from ganglion cells in the salamander retina, the method retrieves the receptive fields of presynaptic bipolar cells, as verified by simultaneous bipolar and ganglion cell recordings. The identified subunit layouts allow improved predictions of ganglion cell responses to natural stimuli and reveal shared bipolar cell input into distinct types of ganglion cells.