The diverse roles of inhibition in identified neural circuits

Inhibitory interneurons represent a diverse population of cell types in the central nervous system, whose general role is to suppress activity of target neurons. The timing of spikes in principal neurons has millisecond precision, and I asked what are the roles of inhibition in shaping the temporal codes that emerge from different parallel local neural circuits. First I investigated the local circuitry of melanopsin-containing ganglion cells in the mouse retina, which are intrinsically photosensitive and responsible for circadian photoentrainment. Using transsynaptic viral tracing, I identified three types of melanopsin-containing ganglion cell, and found that inhibitory (GABAergic) dopaminergic amacrine cells are presynaptic to one of these types. These results provided a direct circuitry link between the medium time scale process of light-dark adaptation, which involves dopamine, and the longer time scale of the circadian rhythm. Next I characterised a subpopulation of genetically-identified neurons in the mouse retina, in order to compare the precise timing of inhibition in different circuits at a high temporal resolution. I identified eight physiologically and morphologically distinct ganglion cell types and found that each circuit could be described by a 'motif' that represented the inhibitory-excitatory interactions that lead to cell-type-specific firing patterns. The cell would fire only when the change in excitation was faster than the change in inhibition. Therefore the role of inhibition is to detect 'irrelevance' in the visual scene, only allowing the ganglion cell to fire at specific time points relating to functions that are both parallel and complementary to the other cell types. Finally, I looked deeper within the neural circuitry of one of the genetically-identified cell types, to study the mechanism of 'fast inhibition' in detecting approaching objects. Through two-photon targeted paired recordings of postsynaptic ganglion cells and presynaptic amacrine cells, I found evidence that the AII amacrine cell - a well-characterised glycinergic inhibitory interneuron known to be involved in night vision circuits - conveys fast inhibitory information to the ganglion cell via an electrical synapse with an excitatory neuron of day vision circuitry only during non-approach motion. Therefore, it appears that the role of inhibition is to dynamically interact with direct excitatory neural pathways during 'irrelevant' stimulation, suppressing or completely blocking activity, resulting in precisely timed spikes that occur in the brief moments when excitation changes faster than inhibition.