Beyond Neurons: Biological INformation processing Systems (BINS)

We can transform our understanding of who we are by catalyzing a new Field: Biological INformation Processing Systems (BINS). We use ‘BINS’ to refer to systems within an organism that transform signals and, in so doing, impact behavior. There is rapidly growing appreciation of the role of non-neural BINS in this process. As one recent example (August 2020 Nature Neuroscience [1]), local perturbation of astrocytes selectively disrupts the recall of remote, but not recent, memories, and the relay of signals between specific brain areas. Astrocytes are a common non-neural cell type in the brain [2], and these findings exemplify an exponential rise in papers addressing ‘astrocytes’ ‘memory’ and ‘behavior’ over the past 25 years (1994-2019). Despite increasing awareness that many other non-neural systems also contribute, there currently is no framework uniting the study of all biological elements contributing to behavior (not only neural). Further, computational modeling—at the biophysical, circuit and cognitive level—almost entirely omits non-neural systems.

Investing now in studies of the non-neural cells and systems that create behavior can focus this momentum, and lead to a more comprehensive and accurate understanding of how our biology creates our actions and identity. This effort will unite distinct elements from several Fields, and advance a re-visioning of Neurology and Psychiatry, consistent with emerging views on the centrality of non-neural systems in diseases including Parkinson’s, ALS and Alzheimer’s Disease.

The Need for this New BINS Field

The perspective outlined here may seem obvious, but there is no macro-structure ‘Field’ that inclusively supports BINS. There are no academic Departments or training programs focused on BINS—where Mycologists, Immunologists, Evolutionary Geneticists, Endocrinologists, Computational Scientists, Applied Mathematicians, Cognitive Scientists and Neuroscientists focus on understanding how biological networks create adaptive behavior, realizing parallels and interdependencies. The lack of an appropriate academic home limits faculty hiring and promotion, a barrier to pursuing BINS research. As importantly, the growth and energy behind any topic are its upcoming scholars: Without training in BINS and recognition by Trainees that there is a Field for them, pursuing this cutting-edge requires a leap of faith. While individual funding opportunities are beginning to emerge, there are no funding mechanisms organized around systematically supporting BINS, nor are there journals or national meetings. The Society for Neuroscience (SfN) catalyzed the discipline of Neuroscience 50 years ago, uniting physiologists, anatomists, and physicists to build new knowledge about neurons and the brain. The emergence of Neuroscience Departments after the founding of the Society [3], organizing brain scientists into a professional discipline, shows the transformative potential of focusing scholarship at pivotal points of the discovery timeline.

In all Fields, increased reliance on formal modeling is a hallmark of theoretical maturation. Catalyzed by investments from the Sloan and Swartz Foundations in Centers for Theoretical Neurobiology, there have been transformative advances in computational neuroscience, and there now exists a rich ecosystem of computational scientists modeling neurons and behavior. However, reflecting the historically-dominant perspective of Neuroscience, almost no models include non-neural elements, let alone focus on them. While important attempts in this direction have occurred [4,5], developing the depth and breadth of the BINS computational community, and supporting young scholars in it, is essential.

A BINS approach is cruicial to understanding the biological basis of behavior

Study of the biological information processing creating behavior is a topic subsumed under the Field Neuroscience, reflecting the central role neurons play. However, this singular orientation is limiting and potentially misleading in two key ways. First, neural information processing requires signals from non-neural generators. Even under a ‘neurocentric’ view, understanding the dynamics of other systems during behavior is essential. Fields such as Neuroendocrinology address components of such interactions, but non-neural regulation goes beyond that coverage, and is not a focus of any single Field. We will not understand neural information processing and its role in behavior without better understanding its non-neural modulators.

Second, non-neural BINS likely conduct computations now attributed only to neurons. These systems act in an internally-coordinated way to transform novel signals, learn, and integrate current context, and these processes create outputs that can drive beneficial behaviors. Candidate non-neural BINS include the vasculature, an electrically active network whose dynamics predict those brain areas processing information [6]. A second example is the choroid plexus. This interconnected epithelial cell network in the middle of the brain, largely devoid of neurons, has recently been shown to have complex calcium dynamics indicative of active signal processing ([7]; Klein et al., in preparation).

References

[1] Kol A, Adamsky A, Groysman M, Kreisel T, London M, Goshen I. 2020. Astrocytes contribute to remote memory formation by modulating hippocampal-cortical communication during learning. Nat Neurosci 23:1229-1239. DOI: 10.1038/s41593-020-0679-6. PMID: 32747787.

[2] Keller D, Erö C, Markram H. 2018. Cell densities in the mouse brain: A systematic review. Front Neuroanat, 12:83. DOI: 10.3389/fnana.2018.00083. PMID: 30405363.

[3] Society for Neuroscience. Surveys of Neuroscience Departments and Programs. Website: https://www.sfn.org/careers/higher-education-and-training/neuroscience-training-program-survey Accessed May 2020.

[4] Merchan L & Nemenman I. 2016. On the sufficiency of pairwise interactions in maximum entropy models of biological networks. J Stat Phys 162:1294-1308. DOI: 10.1007/s10955-016-1456-5

[5] Solé R, Moses M & Forrest S (eds.). 2019. Liquid brains, solid brains. Phil Trans Roy Soc B 374: 20190040. DOI: 10.1098/rstb.2019.0040

[6] Moore CI, & Cao R. 2008. The hemo-neural hypothesis: on the role of blood flow in information processing. J Neurophysiol 99(5):2035-47. DOI: 10.1152/jn.01366.2006 PMID: 17913979

[7] Shipley FB, Dani N, Xu H, Deister C, Cui J, Head JP, Sadegh C, Fame RM, Shannon ML, Flores VI, Kishkovich T, Jang E, Klein EM, Goldey GJ, He K, Zhang Y, Holtzman MJ, Kirchhausen T, Wyart C, Moore CI, Andermann ML, Lehtinen MK. 2020. Tracking calcium dynamics and immune surveillance at the choroid plexus blood-cerebrospinal fluid interface. Neuron S0896-6273(20):30655-3. DOI: 10.1016/j.neuron.2020.08.024. PMID: 32961128.