Concept: Functional Neural Circuits in Interoception Science

Project Concept Review

Council Date: February 7, 2020

Program Officer: Wen G. Chen, Ph.D.

Background

Our body has the ability to sense, interpret, and respond to signals from the external environment, as well as from within itself. Neuroscience has gained a tremendous understanding of how we detect and interact with our external world through research into the primary exteroceptive sensory systems of vision, hearing, olfaction, taste, and somatosensation. We know much less about the interoceptive system—the nervous system’s ability to sense our own internal milieu. On April 16 and 17 of 2019, the National Institutes of Health (NIH) Blueprint for Neuroscience Research Institutes and Centers convened a 2-day workshop on “The Science of Interoception and Its Roles in Nervous System Disorders.” At the workshop, a group of distinguished investigators highlighted recent findings and discussed a wide range of topics critical to the future of interoception research. This workshop addressed some of the key issues in interoception research, including the definition of interoception, the scope of interoception science, interoceptive signaling via specialized interoceptors, specialized ascending and descending neuroanatomical pathways, normative functions and disease implications, potential interventions, as well as the integration of internal and external representations of the world at experimental and computational levels.

After careful considerations, the Blueprint Interoception Working Group has proposed a revised scope to define the field of interoception science. More precisely, interoception science includes studies of processes by which an organism senses, interprets, integrates, and regulates signals from within itself. Here, the action of “sensing” denotes the communication from other physiological systems to the central nervous system, commonly called the ascending pathways; whereas the action of “regulating” refers to the communication from the brain to other physiological systems, the descending pathways. The central nervous system, especially the brain, is primarily responsible for interpreting and integrating the interoceptive signals.

The workshop also identified many critical knowledge gaps and research challenges not currently tackled by major NIH research initiatives, such as the BRAIN Initiative and the NIH Common Fund SPARC Initiative, or by individual NIH neuroscience Institutes and Centers (ICs) through their regular program activities. These critical areas include: 1) functional circuits and interaction dynamics between central and peripheral nervous systems in physiological conditions; 2) the interaction of the interoceptive networks and other sensory, motor, reward, emotional, cognitive/memory circuits to regulate brain diseases and disorders; 3) the impact of central or peripheral disorders on interoceptive networks and the effects of modulating interoceptive processes on the associated diseases and disorders; and 4) the need for objective and quantitative assessments of interoception as well as effective technologies and approaches to modulate interoceptive processes. 

Purpose of Proposed Program

The NIH Blueprint IC Directors requested the Interoception Working Group develop a focused initiative to address the most urgent need of the interoception research. The team has thus proposed and received support from the NIH Blueprint IC Directors to focus the initial effort of interoception science research on functional neural circuits analysis of interoception as it was considered the neural basis of other knowledge gaps. 

The brain communicates with other organs via two major types of pathways, neural pathways and non-neural pathways. The location of the interoceptors may determine whether the interoceptive signals are transmitted through a neural or non-neural pathway. If interoceptors are expressed in neurons located inside the brain, most likely the interoceptive signals are delivered to these neurons through non-neural pathways such as the circulatory system or lymphatic system. In contrast, if interoceptors are expressed in peripheral nerve terminals, they can detect interoceptive signals in local organs directly and induce the peripheral sensory ganglia to generate electrical signals and transmit the information through neural pathways to the brain. There are generally two major types of peripheral sensory ganglia—one residing in the cranial/vagal pathways, such as nodose or jugular ganglia, and often projecting to nucleus tractus solitarii (NTS) of the brainstem; the others are dorsal root ganglia, located along the spinal nerve pathway and projecting into the brain through the spinal cord. Once in the brain, interoceptive information is often first processed in brainstem substructures; the signals then propagate to higher brain regions including hypothalamus, thalamus, insula, anterior cingulate cortex, and somatosensory cortex for further integration and interpretation. In addition, regulating signals may also be generated by neurons inside the brain or the spinal cord in response to the interoceptive input. The regulating signal is then transmitted via non-neural (e.g., humoral) pathways or descending neural pathways (cranial/vagal or spinal efferents) to the effecting organs to modulate their activities or their interoceptive signals. In the neural pathway, the final effecting neurons or effectors, commonly called sympathetic or parasympathetic ganglion neurons, directly synapse with the peripheral organ non-neural cells.  

This concept will focus on the functional neural circuitry analysis of the complete neural circuits connecting between the brain and the rest of body via the neural pathways in animal models. 

Objectives

Examples of the topics of interests include but are not restricted to:

• Cell-type characterization of the peripheral ganglia involved in interoception.
• Identification of specific ganglia responsive to interoceptive signals.
• Anatomical mapping of neural circuits involved in interoception.
• Functional characterizations of interoceptive circuits at physiological and behavioral levels.