Dale's principle and the thermodynamic equilibrium of neural circuits.

Dale’s principle states that neurons in the nervous system have an exclusive physiological effect, each neuron either excites or inhibits all its synaptic targets. It is usually impossible for a neuron to excite some of its targets while inhibiting others. This principle has been known for more than fifty years, and yet there is no explanation for its function. Supported by theoretical analysis and experimental data, I propose that the function of Dale's principle is to maintain thermodynamic equilibrium in neural circuits. I study a nonlinear dynamical model characterized by a given synaptic matrix and input noise. Using the Fokker-Planck equation, I calculate the synaptic matrix consistent with thermodynamic equilibrium, and I show that it must satisfy Dale's principle under quite general assumptions. In order to test the theoretical predictions, I analyze the activity of neurons in the awake primate brain, and I show that collective neural dynamics displays temporal reversibility, which is a hallmark of thermodynamic equilibrium. I conclude by speculating on the significance of equilibrium and reversibility on brain function. While out-of-equilibrium dynamics may better support neural computation, equilibrium represents a desirable "idle" state.