Why an animal needs a brain.

In Principles of Neural Design (2015, MIT Press), inspired by Charles Darwin, Sterling and Laughlin undertook the unfashionable task of distilling principles from facts in the technique-driven, data-saturated domain of neuroscience. Their starting point for deriving the organizing principles of brains are two brainless single-celled organisms, Escherichia coli and Paramecium, and the 302-neuron brain of the nematode Caenorhabditis elegans. The book is an exemplar in how to connect the dots between simpler and (much) more complex organisms in a particular area.

Why I joined the Freedom Rides.

Peter Sterling expands upon his recent Q & A article by discussing his participation in the Freedom Rides and the reasons for his involvement in the civil rights movement.

Peter Sterling.

Interview with Peter Sterling, author of Principles of Neural Design and What Is Health?

Allostasis: A Brain-Centered, Predictive Mode of Physiological Regulation.

Although the concept of allostasis was proposed some 30 years ago, doubts persist about its precise meaning and whether it is useful. Here we review the concept in the context of recent studies as a strategy to efficiently regulate physiology and behavior. The brain, sensing the internal and external milieu, and consulting its database, predicts what is likely to be needed; then, it computes the best response.

Predictive regulation and human design.

Organisms evolving toward greater complexity were selected across aeons to use energy and resources efficiently. Efficiency depended on prediction at every stage: first a clock to predict the planet's statistical regularities; then a brain to predict bodily needs and compute commands that dynamically adjust the flows of energy and nutrients. Predictive regulation (allostasis) frugally matches resources to needs and thus forms a core principle of our design.

How scientists can reduce their carbon footprint.

Cutting down on long-distance air travel is the best way to reduce the emission of greenhouse gases by the scientific community.

Why do axons differ in caliber?

CNS axons differ in diameter (d) by nearly 100-fold (∼0.1-10 μm); therefore, they differ in cross-sectional area (d(2)) and volume by nearly 10,000-fold. If, as found for optic nerve, mitochondrial volume fraction is constant with axon diameter, energy capacity would rise with axon volume, also as d(2).

Natural images from the birthplace of the human eye.

Here we introduce a database of calibrated natural images publicly available through an easy-to-use web interface. Using a Nikon D70 digital SLR camera, we acquired about six-megapixel images of Okavango Delta of Botswana, a tropical savanna habitat similar to where the human eye is thought to have evolved. Some sequences of images were captured unsystematically while following a baboon troop, while others were designed to vary a single parameter such as aperture, object distance, time of day or position on the horizon.

Allostasis: a model of predictive regulation.

The premise of the standard regulatory model, "homeostasis", is flawed: the goal of regulation is not to preserve constancy of the internal milieu. Rather, it is to continually adjust the milieu to promote survival and reproduction. Regulatory mechanisms need to be efficient, but homeostasis (error-correction by feedback) is inherently inefficient.

Cone synapses in macaque fovea: II. Dendrites of OFF midget bipolar cells exhibit Inner Densities similar to their Outer synaptic Densities in basal contacts with cone terminals.

As described in the companion paper, the synaptic terminal of a cone photoreceptor in macaque monkey makes an average of 35 or 46 basal contacts with the tips of the dendrites of its OFF midget bipolar cell. Each basal contact has one or more symmetrically thickened dense regions. These "Outer Densities," averaging 48 or 67 in number, harbor clusters of ionotropic glutamate receptors and are ~0.

Cone synapses in macaque fovea: I. Two types of non-S cones are distinguished by numbers of contacts with OFF midget bipolar cells.

L and M cones, divided into two groups by absorption spectra, have not been distinguished by structure. Here, we report what may be such a difference. We reconstructed the synaptic terminals of 16 non-S cones and the dendritic arbors of their ON and OFF midget bipolar cells from high-magnification electron micrographs of serial thin sections of a small region of macaque fovea.

Retina is structured to process an excess of darkness in natural scenes.

Retinal ganglion cells that respond selectively to a dark spot on a brighter background (OFF cells) have smaller dendritic fields than their ON counterparts and are more numerous. OFF cells also branch more densely, and thus collect more synapses per visual angle. That the retina devotes more resources to processing dark contrasts predicts that natural images contain more dark information.

Design of a trichromatic cone array.

Cones with peak sensitivity to light at long (L), medium (M) and short (S) wavelengths are unequal in number on the human retina: S cones are rare (<10%) while increasing in fraction from center to periphery, and the L/M cone proportions are highly variable between individuals. What optical properties of the eye, and statistical properties of natural scenes, might drive this organization? We found that the spatial-chromatic structure of natural scenes was largely symmetric between the L, M and S sensitivity bands. Given this symmetry, short wavelength attenuation by ocular media gave L/M cones a modest signal-to-noise advantage, which was amplified, especially in the denser central retina, by long-wavelength accommodation of the lens.

How the optic nerve allocates space, energy capacity, and information.

Fiber tracts should use space and energy efficiently, because both resources constrain neural computation. We found for a myelinated tract (optic nerve) that astrocytes use nearly 30% of the space and >70% of the mitochondria, establishing the significance of astrocytes for the brain's space and energy budgets. Axons are mostly thin with a skewed distribution peaking at 0.

Receptive fields and functional architecture in the retina.

Functional architecture of the striate cortex is known mostly at the tissue level--how neurons of different function distribute across its depth and surface on a scale of millimetres. But explanations for its design--why it is just so--need to be addressed at the synaptic level, a much finer scale where the basic description is still lacking. Functional architecture of the retina is known from the scale of millimetres down to nanometres, so we have sought explanations for various aspects of its design.

Loss of sensitivity in an analog neural circuit.

A low-contrast spot that activates just one ganglion cell in the retina is detected in the spike train of the cell with about the same sensitivity as it is detected behaviorally. This is consistent with Barlow's proposal that the ganglion cell and later stages of spiking neurons transfer information essentially without loss. Yet, when losses of sensitivity by all preneural factors are accounted for, predicted sensitivity near threshold is considerably greater than behavioral sensitivity, implying that somewhere in the brain information is lost.

Physiology and morphology of color-opponent ganglion cells in a retina expressing a dual gradient of S and M opsins.

Most mammals are dichromats, having short-wavelength-sensitive (S) and middle-wavelength-sensitive (M) cones. Smaller terrestrial species commonly express a dual gradient in opsins, with M opsin concentrated superiorly and declining inferiorly, and vice-versa for S opsin. Some ganglion cells in these retinas combine S- and M-cone inputs antagonistically, but no direct evidence links this physiological opponency with morphology; nor is it known whether opponency varies with the opsin gradients.

Evidence that vesicles undergo compound fusion on the synaptic ribbon.

The ribbon synapse can release a stream of transmitter quanta at very high rates. Although the ribbon tethers numerous vesicles near the presynaptic membrane, most of the tethered vesicles are held at a considerable distance from the plasma membrane. Therefore, it remains unclear how their contents are released.

Design of a neuronal array.

Retinal ganglion cells of a given type overlap their dendritic fields such that every point in space is covered by three to four cells. We investigated what function is served by such extensive overlap. Recording from pairs of ON or OFF brisk-transient ganglion cells at photopic intensities, we confirmed that this overlap causes the Gaussian receptive field centers to be spaced at approximately 2 SDs (sigma).

Mobility and turnover of vesicles at the synaptic ribbon.

Ribbon synapses release neurotransmitter continuously at high rates, and the ribbons tether a large pool of synaptic vesicles. To determine whether the tethered vesicles are actually released, we tracked vesicles labeled with styryl dye in mouse retinal bipolar cell terminals whose ribbons had been labeled with a fluorescent peptide. We photobleached vesicles in regions with ribbons and without them and then followed recovery of fluorescence as bleached regions were repopulated by labeled vesicles.