Review

Authors: Alireza Azarfar, Niccoló Calcini, Chao Huang...

What any sensory neuron knows about the world is one of the cardinal questions in Neuroscience. Information from the sensory periphery travels across synaptically coupled neurons as each neuron encodes information by varying the rate and timing of its action potentials (spikes). Spatiotemporally correlated changes in this spiking regimen across neuronal populations are the neural basis of sensory representations. In the somatosensory cortex, however, spiking of individual (or pairs of) cortical neurons is only minimally informative about the world. Recent studies showed that one solution neurons implement to counteract this information loss is adapting their rate of information transfer to the ongoing synaptic activity by changing the membrane potential at which spike is generated. Here we first introduce the principles of information flow from the sensory periphery to the primary sensory cortex in a model sensory (whisker) system, and subsequently discuss how the adaptive spike threshold gates the intracellular information transfer from the somatic post-synaptic potential to action potentials, controlling the information content of communication across somatosensory cortical neurons.

Topics: Action Potentials; Animals; Cell Communication; Information Theory; Neurons; Perception; Somatosensory Cortex; Vibrissae

PubMed: 30227142
DOI: 10.1016/j.neubiorev.2018.09.007

Review

Authors: David M Lovinger

Nerve cells (i.e., neurons) communicate via a combination of electrical and chemical signals. Within the neuron, electrical signals driven by charged particles allow rapid conduction from one end of the cell to the other. Communication between neurons occurs at tiny gaps called synapses, where specialized parts of the two cells (i.e., the presynaptic and postsynaptic neurons) come within nanometers of one another to allow for chemical transmission. The presynaptic neuron releases a chemical (i.e., a neurotransmitter) that is received by the postsynaptic neuron's specialized proteins called neurotransmitter receptors. The neurotransmitter molecules bind to the receptor proteins and alter postsynaptic neuronal function. Two types of neurotransmitter receptors exist-ligand-gated ion channels, which permit rapid ion flow directly across the outer cell membrane, and G-protein-coupled receptors, which set into motion chemical signaling events within the cell. Hundreds of molecules are known to act as neurotransmitters in the brain. Neuronal development and function also are affected by peptides known as neurotrophins and by steroid hormones. This article reviews the chemical nature, neuronal actions, receptor subtypes, and therapeutic roles of several transmitters, neurotrophins, and hormones. It focuses on neurotransmitters with important roles in acute and chronic alcohol effects on the brain, such as those that contribute to intoxication, tolerance, dependence, and neurotoxicity, as well as maintained alcohol drinking and addiction.

Topics: Alcoholism; Animals; Brain; Humans; Neurons; Neurotransmitter Agents; Receptors, G-Protein-Coupled; Receptors, Neurotransmitter; Synapses

PubMed: 23584863
DOI: No ID Found

Review

Authors: Klaus M Stiefel, G Bard Ermentrout

Regularly spiking neurons can be described as oscillators. In this article we review some of the insights gained from this conceptualization and their relevance for systems neuroscience. First, we explain how a regularly spiking neuron can be viewed as an oscillator and how the phase-response curve (PRC) describes the response of the neuron's spike times to small perturbations. We then discuss the meaning of the PRC for a single neuron's spiking behavior and review the PRCs measured from a variety of neurons in a range of spiking regimes. Next, we show how the PRC can be related to a number of common measures used to quantify neuronal firing, such as the spike-triggered average and the peristimulus histogram. We further show that the response of a neuron to correlated inputs depends on the shape of the PRC. We then explain how the PRC of single neurons can be used to predict neural network behavior. Given the PRC, conduction delays, and the waveform and time course of the synaptic potentials, it is possible to predict neural population behavior such as synchronization. The PRC also allows us to quantify the robustness of the synchronization to heterogeneity and noise. We finally ask how to combine the measured PRCs and the predictions based on PRC to further the understanding of systems neuroscience. As an example, we discuss how the change of the PRC by the neuromodulator acetylcholine could lead to a destabilization of cortical network dynamics. Although all of these studies are grounded in mathematical abstractions that do not strictly hold in biology, they provide good estimates for the emergence of the brain's network activity from the properties of individual neurons. The study of neurons as oscillators can provide testable hypotheses and mechanistic explanations for systems neuroscience.

Topics: Action Potentials; Animals; Biological Clocks; Humans; Models, Neurological; Neurons

PubMed: 27683887
DOI: 10.1152/jn.00525.2015

Review

Authors: Alexei Verkhratsky, Margaret S Ho, Vladimir Parpura...

As the nervous system evolved from the diffused to centralised form, the neurones were joined by the appearance of the supportive cells, the neuroglia. Arguably, these non-neuronal cells evolve into a more diversified cell family than the neurones are. The first ancestral neuroglia appeared in flatworms being mesenchymal in origin. In the nematode C. elegans proto-astrocytes/supportive glia of ectodermal origin emerged, albeit the ensheathment of axons by glial cells occurred later in prawns. The multilayered myelin occurred by convergent evolution of oligodendrocytes and Schwann cells in vertebrates above the jawless fishes. Nutritive partitioning of the brain from the rest of the body appeared in insects when the hemolymph-brain barrier, a predecessor of the blood-brain barrier was formed. The defensive cellular mechanism required specialisation of bona fide immune cells, microglia, a process that occurred in the nervous system of leeches, bivalves, snails, insects and above. In ascending phylogeny, new type of glial cells, such as scaffolding radial glia, appeared and as the bran sizes enlarged, the glia to neurone ratio increased. Humans possess some unique glial cells not seen in other animals.

Topics: Animals; Biological Evolution; Caenorhabditis elegans; Humans; Myelin Sheath; Neuroglia; Neurons; Oligodendroglia

PubMed: 31583583
DOI: 10.1007/978-981-13-9913-8_2

Review

Authors: Vanessa Lanoue, Helen M Cooper

A neuron's contribution to the information flow within a neural circuit is governed by the structure of its dendritic arbor. The geometry of the dendritic arbor directly determines synaptic density and the size of the receptive field, both of which influence the firing pattern of the neuron. Importantly, the position of individual dendritic branches determines the identity of the neuron's presynaptic partner and thus the nature of the incoming sensory information. To generate the unique stereotypic architecture of a given neuronal subtype, nascent branches must emerge from the dendritic shaft at preprogramed branch points. Subsequently, a complex array of extrinsic factors regulates the degree and orientation of branch expansion to ensure maximum coverage of the receptive field whilst constraining growth within predetermined territories. In this review we focus on studies that best illustrate how environmental cues such as the Wnts and Netrins and their receptors sculpt the dendritic arbor. We emphasize the pivotal role played by the actin cytoskeleton and its upstream regulators in branch initiation, outgrowth and navigation. Finally, we discuss how protocadherin and DSCAM contact-mediated repulsion prevents inappropriate synapse formation between sister dendrites or dendrites and the axon from the same neuron. Together these studies highlight the clever ways evolution has solved the problem of constructing complex branch geometries.

Topics: Animals; Dendrites; Humans; Neurogenesis; Neuronal Plasticity; Synapses

PubMed: 30550882
DOI: 10.1016/j.ydbio.2018.12.005

Review

Authors: Iris Reuveni, Edi Barkai

The activity of a neural network is a result of synaptic signals that convey the communication between neurons and neuron-based intrinsic currents that determine the neuron's input-output transfer function. Ample studies have demonstrated that cell-based excitability, and in particular intrinsic excitability, is modulated by learning and that these modifications play a key role in learning-related behavioral changes. The field of cell-based plasticity is largely growing, and it entails numerous experimental findings that demonstrate a large diversity of currents that are affected by learning. The diverse effect of learning on the neuron's excitability emphasizes the need for a framework under which cell-based plasticity can be categorized to enable the assessment of the computational roles of the intrinsic modifications. We divide the domain of cell-based plasticity into three main categories, where the first category entails the currents that mediate the passive properties and single-spike generation, the second category entails the currents that mediate spike frequency adaptation, and the third category entails a novel learning-induced mechanism where all excitatory and inhibitory synapses double their strength. Curiously, this elementary division enables a natural categorization of the computational roles of these learning-induced plasticities. The computational roles are diverse and include modification of the neuronal mode of action, such as bursting, prolonged, and fast responsive; attention-like effect where the signal detection is improved; transfer of the network into an active state; biasing the competition for memory allocation; and transforming an environmental cue into a dominant cue and enabling a quicker formation of new memories.

Topics: Adaptation, Physiological; Animals; Humans; Learning; Neuronal Plasticity; Neurons; Synaptic Potentials

PubMed: 29947597
DOI: 10.1152/jn.00102.2018

Review

Authors: Sydney S Cash, Leigh R Hochberg

Single neuron actions and interactions are the sine qua non of brain function, and nearly all diseases and injuries of the CNS trace their clinical sequelae to neuronal dysfunction or failure. Remarkably, discussion of neuronal activity is largely absent in clinical neuroscience. Advances in neurotechnology and computational capabilities, accompanied by shifts in theoretical frameworks, have led to renewed interest in the information represented by single neurons. Using direct interfaces with the nervous system, millisecond-scale information will soon be extracted from single neurons in clinical environments, supporting personalized treatment of neurologic and psychiatric disease. In this Perspective, we focus on single-neuronal activity in restoring communication and motor control in patients suffering from devastating neurological injuries. We also explore the single neuron's role in epilepsy and movement disorders, surgical anesthesia, and in cognitive processes disrupted in neurodegenerative and neuropsychiatric disease. Finally, we speculate on how technological advances will revolutionize neurotherapeutics.

Topics: Brain; Epilepsy; Humans; Movement Disorders; Neurology; Neurons

PubMed: 25856488
DOI: 10.1016/j.neuron.2015.03.058

Review

Authors: Kelsie Eichel, Kang Shen

Neurons are highly polarized cells with extensive axonal and dendritic projections that send and receive signals over long distances. Neuronal polarity requires sorting and maintaining a unique set of proteins to the neuron's distinct axonal and somatodendritic domains. The axon initial segment (AIS) is a specialized subcellular region located between these two domains and is critical for neuronal polarity. The AIS has a complex and elaborately organized molecular structure that enables its functions in neuronal polarity. Disruption of the AIS is associated with neurodevelopmental and neuropsychiatric disease pathologies, thus highlighting the importance of the AIS in neuronal physiology. This review discusses recent progress toward understanding the molecular architecture of the AIS and its importance in neuronal polarity through regulating protein diffusion and vesicular trafficking.

Topics: Axon Initial Segment; Axons; Cell Polarity; Neurons; Protein Transport

PubMed: 35640681
DOI: 10.1016/j.ydbio.2022.05.016

Review

Authors: Lukas Fischer, Raul Mojica Soto-Albors, Vincent D Tang...

Dendrites receive the vast majority of a single neuron's inputs, and coordinate the transformation of these signals into neuronal output. and theoretical evidence has shown that dendrites possess powerful processing capabilities, yet little is known about how these mechanisms are engaged in the intact brain or how they influence circuit dynamics. New experimental and computational technologies have led to a surge in interest to unravel and harness their computational potential. This review highlights recent and emerging work that combines established and cutting-edge technologies to identify the role of dendrites in brain function. We discuss active dendritic mediation of sensory perception and learning in neocortical and hippocampal pyramidal neurons. Complementing these physiological findings, we present theoretical work that provides new insights into the underlying computations of single neurons and networks by using biologically plausible implementations of dendritic processes. Finally, we present a novel brain-computer interface task, which assays somatodendritic coupling to study the mechanisms of biological credit assignment. Together, these findings present exciting progress in understanding how dendrites are critical for learning and behavior, and highlight how subcellular processes can contribute to our understanding of both biological and artificial neural computation.

Topics: Dendrites; Pyramidal Cells; Neurons; Hippocampus; Learning; Models, Neurological; Action Potentials

PubMed: 36351832
DOI: 10.1523/JNEUROSCI.1132-22.2022

Review

Authors: Keith May, Li Zhaoping

Li and Atick (Network: Computation in Neural Systems 5 (1994) 157-174) presented a theory of efficient binocular encoding that explains a number of experimental findings. A binocular neuron is conventionally described in terms of two channels: the left and right eyes. Li and Atick's theory instead describes the neuron in terms of two alternative channels: the binocular sum and difference. The advantage of the latter description is that, unlike the left and right eye channels, the summation and differencing channels are usually uncorrelated; this means that each channel can be optimised independently of the other. The theory shows how to derive optimal receptive fields for the binocular summation and differencing channels; from these, it is easy to derive the neuron's optimal left and right eye receptive fields. The functional reality of the summation and differencing channels is demonstrated by a series of adaptation studies that confirm some counterintuitive predictions of the theory. Here we provide an accessible account of the theory, and review the evidence supporting it.

Topics: Humans; Eye; Neurons; Vision, Binocular

PubMed: 36216600
DOI: 10.1016/j.visres.2021.08.005