Jonas review on PV+ interneurons in Science

In a review in Science (DOI 10.1126/science.1255263), Peter Jonas, Professor at IST Austria, and his postdocs Hua Hu and Jian Gan review the role of fast-spiking, parvalbumin-expressing (PV+) interneurons. Over the past 20 years, neuroscientists have obtained extensive knowledge about PV+ interneurons, offering the possibility that neuroscientists might be able to close the gaps between molecular, cellular, network and behavioral levels of understanding. The hallmark property of PV+ interneurons is fast signal propagation. In their review, Peter Jonas and colleagues explore how this remarkable speed arises from the molecular and cellular properties of these interneurons, and how it contributes to neuronal network operations and brain diseases.

PV+ interneurons form only a small minority (approx. 2.6%) of all neurons in the brain. The vast majority are glutamatergic principal neurons, while inhibitory GABAergic interneurons, of which the PV+ interneurons are a subtype, constitute 10-20% of all neurons. PV+ interneurons might appear exotic, but are well studied because they can be reliably identified under experimental conditions. To understand the function of PV+ interneurons, Peter Jonas and colleagues first focus on their structure. PV+ interneurons have multiple long dendrites to acquire input from many principal neurons. Furthermore, the axons branch extensively, so that PV+ interneurons generate a massive inhibitory output on other neurons. Physiologically, the K+ (potassium ion) channels of PV+ interneuron dendrites allow the interneurons to sample activity from a range of principal neurons and promote the quick initiation of an action potential, the nerve impulse. Axons promote action potentials, the nerve impulses, reliably, quickly and frequently because of an excessively high density of Na+ (sodium ion) channels. In response to an action potential, the neurotransmitter GABA is released quickly into the synapse as PV+ interneuron synapses are optimized for speed. Some of these intriguing properties were discovered by the Jonas group at IST Austria over the last three years.

Peter Jonas and colleagues then explore the roles PV+ interneurons play in neuronal networks, higher brain functions, behavior and disease. In microcircuits, the fast signaling mechanism of PV+ interneurons is important for their role in feedforward and feedback inhibition. The latter implements a “winner takes all” mechanism: once the principal neurons with the strongest input in the microcircuit fire, all others are inhibited and cannot signal. This contributes to advanced computations in microcircuits and neuronal networks. Because of detailed knowledge about the PV+ interneurons, Peter Jonas and colleagues can address the question of how this neuron type shapes higher brain function and animal behavior. They survey that PV+ interneurons are involved in pattern separation, modulation of place and grid field interneurons, modulation of sensory responses, and the regulation of plasticity and learning. Also, in many neurological and psychiatric diseases, including epilepsy, schizophrenia, depression, autism, and Alzheimer’s disease, the function of PV+ interneurons is changed. Although we now have extensive and detailed knowledge on PV+ interneurons, much remains to be learned about their basic function before PV+ interneurons may be used for therapeutic purposes.