Neurons; Synapses; Glial Cells

All functions of consciousness are mediated by neurons and synapses and their supporting cells and structures. The dynamic core of active neurons mediates the emergent property of consciousness.

Neurons have thousands, sometimes tens of thousands, of synapses, spaced along the branches of the dendrites. (Hawkins - A Thousand Brains, 44)

The activity of a neuron in a neuronal network depends both on the synaptic input it receives and on its own intrinsic electrical characteristics. (Arbib, Handbook of Brain Theory; Abbott; Activity Neuronal, 63)

The intrinsic characteristics of individual neurons can be modified by activity. (Abbott; Activity Neuronal, 63)

Roughly a dozen different types of ion channels contribute to the membrane conductance of a typical neuron. (Abbott; Activity Neuronal, 63)

A complex array of biochemical processes controls the number and distribution of ion channels by constructing and transporting channels, modulating their properties, and inserting them into and removing them from the plasma membrane. (Abbott; Activity Neuronal, 63)

Many of the biochemical processes of neurons are affected by electrical activity, ranging from activity-induced gene expression to activity-dependent modulation of assembled ion channels. (Abbott; Activity Neuronal, 63)

Motor neurons, which relay neural commands to drive skeletal muscle movements, encompass types ranging from “slow” to “fast,” whose biophysical properties govern the timing, gradation, and amplitude of muscle force. Slow motor neurons, which possess low activation thresholds and long afterhyperpolarizations, can sustain long periods of low-frequency firing. Fast motor neurons, in contrast, are larger, exhibit high activation thresholds with shorter afterhyperpolarizations, and can fire in high-frequency bursts.

The time it takes the body of a neuron to integrate incoming information is long compared with the time it takes a pulse to propagate between neurons. This time for processing of input information by each neuron sets the rate at which a network of neurons can function. (Holland; Emergence, 85)

Once a nerve cell has become differentiated, it does not divide anymore. A single nucleus, with the same DNA, must serve an entire lifetime for the formation and maintenance of tens of thousands of synapses. (Changeux; Neuronal Man, 206)

Glial Cells

Research Study — Glia as Architects of Central Nervous System

Research Study — Cell Types across Neocortical Areas

Research Study — NMDA Receptor Ion Channel Crystal Structure

Research Study — Neuron Axon Myelin Distribution

Information Representation in the Neural Network

Information in the neural network is represented by neural activity patterns comprised of neural signals following pathways along neuron axons connected by the most efficacious synapses.

Information is contained in the patterns of neuronal excitation. (Sapolsky; Biology and Human Behavior, 1-26)

Neurons from different networks can overlap and be used in different settings. (Sapolsky; Biology and Human Behavior, 1-26)

Because principal neurons frequently discharge in bursts of action potentials, the degree of postsynaptic facilitation or depression during such bursts may contain much of the information transmitted through the network. (Andersen; Hippocampus Book, 211)

One neuron or group of neurons can be part of many networks, and thus many representations of memory, perception, or action. (Fuster; Prefrontal Cortex, 379)

Widespread and sparse neural patterns, ever changing on the basis of a few milliseconds, imply that the neural network is highly differentiated and highly integrated, yielding high complexity for the dynamic core.

A dynamic network of neurons and synapses provide a mechanism for the brain's information machine. Although there are many slightly different morphologies and functionality variations among neurons, they can be considered in two broad classes of projection neurons and interneurons. The neural network contains about 10¹² neurons and 10¹⁵ synapses. Each projection neuron's dendritic tree has about 10⁴ synapses, and the neuron communicates with about 10⁴ other neurons, although not directly; the communication with 10⁴ other neurons will be via multi-synaptic connections in the neural network.

Principal Neurons and Interneurons

Neurons of the cerebral cortex are of two functional categories: (1) principal (projection) neurons and (2) interneurons. (Afifi; Functional Neuroanatomy, 339)

Projection neurons and interneurons. (LeDoux; Synaptic Self, 50) (Changeux; Neuronal Man, 51) (Searle; Mystery of Consciousness, 27)

Two main groups of neurons are present within the cortex; the most numerous group (approximately 80%) are excitatory in their influence on other cells and are characterized morphologically by having small spines on their dendritic surfaces that act as specialized sites for synaptic contact. (Arbib, Handbook of Brain Theory; Lund; Visual Cortex Cell Types, 1016)

The less numerous (20%) group of cortical neurons, the interneurons, are generally stellate in morphology, but largely lack dendritic spines, contain GABA as their synaptic transmitter and are inhibitory in their output to other cells. (Lund; Visual Cortex Cell Types, 1016)

A projection neuron typically has thousands of synapses on its dendritic tree; also, its axon may have a number of collateral branches, almost always using the excitatory neurotransmitter glutamate.

Interneurons, which are of many subtypes, connect projection neurons, providing mostly logical functions via the inhibitory neurotransmitter GABA.

Link to — Dendritic Trees

Some neurons, local interneurons, have short axons and make connections to cells in their immediate vicinity, while others, projection neurons, send their axons to distant targets. (Sanes; Development of the Nervous System, 111)

Projection neurons tend to be idle in the absence of inputs. Inhibitory interneurons are often active all the time. (LeDoux; Synaptic Self, 50)

Cerebral cortex has its full complement of neurons (10 to 20 billion) by the 18th week of intrauterine life. (Afifi; Functional Neuroanatomy, 339)

The CA1 pyramidal neuron is arguably the most extensively studied neuron with respect to resting membrane properties, dendritic function, and synaptic integration. (Andersen; Hippocampus Book, 152)

Anatomically, interneurons represent one of the most diverse populations in the mammalian CNS. (Andersen; Hippocampus Book, 179)

Research study — Brain and Spinal Cord Cell Profiling with Barcoding

Research Study — Interneuron Diversity, Early Emergence

Research Study — Interneuron Developmental Diversification

Research Study — Astrocyte Morphogenesis and Synaptogenesis

Research Study — Neuronal Diversity

Research Study — Nervous System Reprogrammed from One Cell Type to Another — Neurons specialize into an astonishing diversity of classes. Suites of factors can convert non-neuronal cells into induced neuronal cells showing class-specific features.

Pulsate Nature of Neural Network Activity

Information flow in neurons and neuronal networks is not instantaneous. It takes time for action potential to propagate along axons and for neurotransmitters to span the synaptic cleft and activate the postsynaptic neuron.

The state of individual synapses changes on the basis of about 4 ms.

The propagation time and responses of neurons and synapses results in pulsate behavior of the neuronal network.

Neurons are coincidence detectors — they respond to a population of input spikes above threshold.

The neural network is characterized by reentrant signals (positive feedback) resulting in recursive updating of the synaptic state of the network on the basis of about 100 to 500 ms.

Consciousness is mediated by the momentary state of active synapses in the neuronal network.

The state of the dynamic core mediating an instantaneous thought changes and is updated via the recursive functionality of the neuronal network.

Quorum of Input Signals Causes a Neuron to Fire

A neuron will fire whenever a quorum of input signals on its ~10,000 dendrite tree synapses is achieved in a ~2 ms time window. Generally, the input signals comprising the quorum can occur on the synapses in any combination; no particular combination is required. Consequently, a neuron's functionality is stochastic, not deterministic.

Presynaptic neuron connections require that perhaps 50--100 excitatory neurons fire together to produce a synaptic potential large enough to trigger an action potential. (Kandel; Principles of Neural Science, 207)

Dendritic Tree Synaptic Efficacies Molded by Experience

As a result of synaptic plasticity, the efficacies of synapses on a network of dendritic trees will achieve a pattern of efficacies corresponding to the input signal patterns the dendritic tree synapses have experienced in the past. This plasticity of the synapses and memory for input signal patterns contributes to an associative memory function. In this way, a neural network of many millions of dendritic trees becomes ever more sensitive to the input signal patterns it has received in the past.

Note, however, the prevalent degeneracy in input signal sensitivity. No particular combination of active synapses is required. Each time a memory is reconstructed a slightly different set of many millions of efficacious synapses will be activated.

Research study — Dendritic Spines and Memories — in the mouse cortex, learning and novel sensory experience lead to spine formation and elimination by a protracted process.

Research Study — Dendritic Field Orientation Toward Active Axons in Developing Cortex — regulation of dendrite orientation is conserved across species and cortical areas and shows how high-acuity sensory function may be achieved by the tuning of subcellular polarity to sources of high sensory activity.

Action Potential Triggered at Axon Hillock by Quorum Sensing of Dendritic Tree Synapses

Action potential is generated in the initial part of the axon where it connects with the cell body. (LeDoux; Synaptic Self, 47)

A projection neuron typically has about 10,000 synapses on its dendritic tree; also, its axon may have a number of collateral branches.

Each neuron receives about 10⁴ synapses and communicates with about 10⁴ other neurons [although not directly; the communication with 10⁴ other neurons will be via multi-synaptic connections in the neural network]. (Koch, Neuronal Theories; Stevens; Cortical Theory, 242)

A neuron fires whenever its quorum of input signals (excitatory and inhibitory) exceeds its firing threshold in a ~2 ms time window. Consequently, a neuron will fire at a rate between its intrinsic quiescent low-level of a few Hertz to a maximum rate of about 100 Hz.

Quorum sensing of inputs from dendritic tree synapses (~10,000 synapses) determine triggering of neuron firing in a sliding ~2 ms time window

Rate at which a cell fires spontaneously is a function of certain electrical and chemical characteristics of the cell. (LeDoux; Synaptic Self, 64)

Neurons in the sensory areas of the brain typically fire at high rates (0-100 Hz), whereas neurons in the prefrontal cortex at a lesser rate (0-10 Hz). (Edelman; Universe of Consciousness, 169)

Almost Poisson nature of the spike trains of single neurons found in most brain areas. (Rolls; Memory, Attention, and Decision-Making, 72)

Cell's intrinsic properties, which may have a strong genetic component, will greatly influence everything a cell does. (LeDoux; Synaptic Self, 64)

Neuron Configuration, Size, Shape

Unlike most of the cells of the body, which have a simple shape, nerve cells have highly irregular shapes and are surrounded by a multitude of exceedingly fine extensions of axons and dendrites. (Kandel; Search of Memory, 61)

Estimated to be many hundreds of different neuronal types, far more than in any other organ of the body. (Kandel; Principles of Neural Science, 1019)

Neurons show enormous variety in cellular anatomy, physiological function, neural chemistry, and conductivity. (Sanes; Development of the Nervous System, 87)

Axons and dendrites are extremely thin (about 10^-2 the thickness of a human hair). (Kandel; Search of Memory, 62)

A neuron may be innervated by as many as 10,000 different synaptic endings. (Kandel; Search of Memory, 222)

Some nerve connections are located nearly a meter from the cell bodies of origin. (Kandel; Search of Memory, 335)

Postsynaptic Density (PSD) at Spines

A prominent feature of almost all spines throughout the nervous system is a postsynaptic density (PSD), an electron-dense thickening of the postsynaptic membrane. (Andersen; Hippocampus Book, 137)

Functionally, the PSD is a biochemical specialization that allows numerous molecules (e.g. receptors, kinases, cytoskeletal elements) to be associated in a structured array at the synapse. (Andersen; Hippocampus Book, 137)

Dendritic spines are not static structures; rather, their shape is determined from moment to moment by the dynamics of the actin cytoskeleton. (Andersen; Hippocampus Book, 397)

Dendrites are able to generate a variety of active responses, including back-propagating action potentials and dendritic Na+ and Ca2+ spikes. (Andersen; Hippocampus Book, 152)

The neuron appears to compensate for voltage attenuation in dendrites by at least two key mechanisms: (1) synapse conductance scaling, and (2) excitable dendrites containing myriad voltage-gated channels. (Andersen; Hippocampus Book, 152)

NMDA receptors, which mediate a slow synaptic current, blocked in a voltage-dependent manner, occupy a disk-like space near the center of the PSD. (Andersen; Hippocampus Book, 137)

AMPA receptors, which mediate a fast synaptic current, are distributed more evenly throughout the PSD. (Andersen; Hippocampus Book, 137)

Generally, each neuron lasts a lifetime

Large Nerve Cells

Purkinje cells are the largest nerve cells in the brain. (Llinás; I of the Vortex, 46)

Motor neurons of the spinal cord have many branching dendrites that extend in all directions, and a single long axon that extends very long distances to innervate skeletal muscles. (Eichenbaum; Neuroscience of Memory, 31)

A neuron receives many excitatory and inhibitory inputs form many other cells; the likelihood of firing at any one moment depends on the net balance between excitation and inhibition across all of the inputs at that particular time. (LeDoux; Synaptic Self, 55)

Most Nerve Cells Fire All the Time

Most nerve cells in the brain fire all the time, all day and all night. (Hobson; Dreaming as Delirium, 28)

When nothing much is happening, a neuron usually sends spikes down its axon at a background rate between 1 and 5 Hz. When a neuron becomes excited, because it receives many excitatory signals, its firing rate increases to 50-100 Hz or more. For short intervals, a neuron's firing rate may reach 500 Hz. (Crick; Astonishing Hypothesis, 92)

Layer 5 neurons fire in bursts of a few spikes at rates at least as high as 250 Hz, with intrinsic intrabursts firing rates on the order of 15 Hz. (Baars, Essential Sources in Scientific Consciousness 68; LaBerge; Attention, the Triangular Circuit, 300)

Since a neuron fires stochastically in response to a quorum of combined excitatory and inhibitory input signals on the ~10⁴ synapses of its dendritic tree, the neuron will fire stochastically at a rate between its quiescent rate and its maximum rate.

Most neurons in the brain are under the influence of as many as a dozen or more neuroactive substances. (Shepherd, Synaptic Organization of the Brain; McCormick; Neurotransmitter Actions, 61)

Neurons generate strong electrical impulses (spikes) when they received enough excitatory inputs from their connected neurons. These spikes cause a release of neurotransmitter molecules at the synaptic connections with other neurons, which triggers an electrical impulse in postsynaptic cells. Neurons can excite each other so that each spike in one neuron causes an increasing number of other neurons to degenerate spikes, even in the absence of external stimulation. This growth of activity in a population of strongly interacting neurons increases until some regulatory mechanisms stabilizes a constant average neuronal activity.

Most Nerve Pulses about the Same Size and Shape

Pulses throughout the CNS are pretty much the same size; amplitude carries little information beyond the presence or absence of a pulse. (Holland; Emergence, 85)

If enough pulses arrive at the surface of a neuron during a short interval of time, the neuron fires, propagating a new pulse down its own axon. (Holland; Emergence, 85)

Neurons are coincidence detectors: large numbers of other cells connect to them. (Zeman; Consciousness, 295)

Variable Discharge Bursting Properties of Hippocampal Neurons

Electrophysiological behavior of the different neurons in the hippocampus is variable. Dentate granule and CA1 pyramidal neurons can fire repetitively at up to several hundred Hz. CA3 pyramidal neurons tend to fire in short bursts of 5-10 action potentials. Bursting properties of CA3 hippocampal neurons are thought to be important for explaining the seizure susceptibility of the hippocampus. (Shepherd, Synaptic Organization of the Brain; Johnston; Hippocampus, 438)

Research Study — Variable Discharge of Cortical Neurons — Cortical neurons generally perform simple algebra resembling averaging,but more sophisticated computations arise by virtue of theanatomical convergence of novel combinations of inputs to thecortical column.

Principal Neurons

Five main principle-cell types have distinct functional properties. (Buzsáki; Rhythms of the Brain, 67)

Distinct functional properties of principle-cell types result from the unique combination of ion channels in the membrane and from their morphological individuality. (Buzsáki; Rhythms of the Brain, 67)

Projection neurons have relatively long axons that extend out of the area in which their cell bodies are located. (LeDoux; Synaptic Self, 49)

Pyramidal neurons are the principal neuron in all three basic types of cortex: olfactory, hippocampal, and neocortex. (Shepherd; Synaptic Organization of the Brain, 25)

Pyramidal neurons

Pyramidal neurons -- apex of the pyramid is directed toward the cortical surface. Each pyramidal neuron has an apical dendrite directed toward the surface of the cortex and several horizontally oriented basal dendrites that arise from the base of the pyramid. (Afifi; Functional Neuroanatomy, 339)

Pyramidal neurons feature a long axon that gives off collaterals that make synapses on targets within the neighborhood of the cell and at different distances from the cell. (Shepherd and Koch; Synaptic Circuits, 25)

A pyramidal neuron may branch to several cortical areas and make synaptic connections to a multitude of neurons. (Koch, Neuronal Theories; Van Essen; Dynamic Routing Strategies, 288)

Pyramidal neurons are found in all cortical areas except layer 1. They vary in size; most are between 10 and 50 µm in height. (Afifi; Functional Neuroanatomy, 339)

Interneurons

Interneurons link their short axons to nearby neurons, often projection neurons, and are involved in information processing. (LeDoux; Synaptic Self, 49)

Organization of interneurons in the spinal cord for vertebrates is quite complex. (Kandel; Principles of Neural Science, 1248)

Interneurons synapse with each other and with principle cell dendrites in inhibitory dendrodendritic profiles. (LaBerge; Attentional Processing, 178)

Using numerous classes of GABAergic inhibitory interneurons enormously multiplies the functional repertoire of principle cells, using mostly local interneuron wiring. (Buzsáki; Rhythms of the Brain, 68)

GABA is largely a local transmitter, which serves interneurons and acts for the most part upon neighboring cells. (Fuster; Prefrontal Cortex, 65)

Mutual inhibitory connections synchronize interneurons, producing oscillations at various frequencies, including theta (5 Hz) and gamma (40 Hz) frequencies. (Johnston; Hippocampus, 423)

Two firing patterns that are characteristic of interneurons are fast spiking (FS) and low-threshold spiking (LTS). (Traub; Cortical Oscillations, 182)

Research study — Interneuron Activity-Dependent Mechanisms Specify Neuronal Properties

Research study — Dendritic Mechanisms in Interneurons

Research study — Cortical Interneurons that Specialize in Disinhibitory Control

Research study — Interneuron Developent Cell Death Intrinsically Determined — Either a cell-autonomous or population-autonomous mechanism could explain why cell death occurred at a constant rate across broad range of interneuron transplant sizes.

Inhibition and Recurrent Collateral Projections Sharpen Signals

Neurons sharpen the detection of signals by inhibiting themselves and other neurons. (Sapolsky; Biology and Human Behavior, 1-25)

The ability of neurons to have projections coming off the axon and sending projections back onto themselves (called recurrent collateral projections) allows them to inhibit themselves and sharpen their signals over time. (Sapolsky; Biology and Human Behavior, 1-25)

Recurrent collateral projections are seen in many neurons. (Sapolsky; Biology and Human Behavior, 1-25)

Through lateral inhibition, neurons sharpen their signals over space. (Sapolsky; Biology and Human Behavior, 1-25)

Ionic channels in neurons

Because ions are unequally distributed across the membrane, they tend to diffuse down their concentration gradient through ionic channels. (Shepherd; Synaptic Organization of the Brain, 38)

Ionic channels that conduct Ca²⁺ are present in all neurons. (Shepherd; Synaptic Organization of the Brain, 50)

Direct and Indirect Gating of Ion Channels

Direct gating of ion channels through the ionotropic receptors is usually rapid -- on the order of milliseconds -- because it involves a change in the conformation of only a single macromolecule. (Kandel; Principles of Neural Science, 240)

Indirect gating of ion channels through metabotropic receptors is slower in onset (tens of milliseconds to seconds) and longer lasting (seconds to minutes) because it involves a cascade of reactions. (Kandel; Principles of Neural Science, 240)

Gap junctions between neurons

Gap junctions are actual physical connections between neighboring neurons made by large macromolecules that extend through the membranes of both cells and contain water-filled pores. Gap junctions allow for the direct exchange of ions and other small molecules between cells. (Shepherd; Synaptic Organization of the Brain, 57)

Gap junction channels, direct flow of current from cell to cell, rapid and synchronous firing of interconnected cells. (Llinás; I of the Vortex, 90)

Gap junction (Koch; Quest for Consciousness, 36)

Ephaptic interactions between neurons

Ephaptic interactions refer to interactions between neurons based largely upon their close physical proximity. The flow of ions into and out of one neuron will set up local electrical currents that can partially pass through neighboring neurons. (Shepherd; Synaptic Organization of the Brain, 58)

In regions that possess closely spaced neuronal elements, such as the close packing of cell bodies in hippocampus and cerebellum or the bundling of dendrites in the cerebral cortex, there is a possibility of significant ephaptic interaction. (Shepherd; Synaptic Organization of the Brain, 58)

Firing rate of neurons

Firing rate of a neuron is an ever-changing dynamic value that depends upon the momentary participation of the neuron in a neuronal assembly.

Neurons in the sensory areas of the brain typically fire at high rates (0-100 Hz), whereas neurons in the prefrontal cortex at a lesser rate (0-10 Hz). (Edelman; Universe of Consciousness, 169)

Research Study — Fast Vesicle Reloading Sustains High Bandwidth

Neuron signals: firing rate; fine temporal structure

Two aspects of neuron signals in the brain: (1) rate or mean frequency of firing, (2) fine temporal signal structure, which is evaluated in terms of correlations among sets of cells. (Llinas, Mind-Brain Continuum; von der Malsburg; Binding Problem, 137)

A neuron firing at five times per second can reflect a neuron discharge every 200 ms or, alternatively, a cell that fires a burst of five discharges during an initial 200 ms, followed by 800 ms of silence. (Squire; Fundamental Neuroscience, 187)

“Spikes” of Action Potential

Neurons communicate in pulses of electrical potential traveling down an axon. Each neuron can have inputs from thousands of other neurons linked via dendrites on the neuron’s cell body. Some of these input neurons will be excitatory and others will be inhibitory. The spike of voltage from each incoming neuron will persist for only a millisecond of so. For a neuron to fire a spike of its own, the incoming excitatory and inhibitory spikes must produce an appropriate spike-combination above threshold, with the array of spikes coincident in a brief, few-millisecond time interval.

Rate Coding in Cortex

Neural Network — Rate Coding in Cortex

Neurons fire even in quiescent state, and about 100 pulses/sec when active

A typical neuron in a quiescent state will fire at a rate of a few pulses per second. When active, a neuron will typically fire at rates up to about 100 pulses per second. At highest activity, a neuron may fire about 500 pulses per second.

Pulse-like behavior of neurons and the neural network

Thousands of spines on is dendritic tree comprise the input terminals of a neuron. Thousands of other neurons and their axons form synapses with these dendrites. Some of these input axons are excitatory, some are inhibitory, and some are modulatory. The neural signals incoming to the receptors are brief (a millisecond or so) and must be considered as pulses. If the summation of these incoming pulses exceeds a momentary threshold at the neuron’s soma, the neuron will “fire” a signal down its axon.

Two thirds of neurons often fire in bursts of 2-4 spikes within 2-6 msec and show a small peak in the 25-50 Hz band of the power spectrum that is related to the propensity of spikes to fire in bursts. The statistical properties can be fitted by Poisson-distributed bursts with a burst-dependent refractory period. The remaining third of the cells have an autocorrelation function and an interspike interval distribution compatible with the notion that spikes are Poisson distributed with a refractory period. (Koch, Neuronal Theories; Koch and Crick; Neuronal Basis, 104)

Oscillatory nature of some neurons

Inferior Olive neurons

Neural thresholds and Priming

Koch, 198

The neurons of some modules such as basal ganglia normally fire in an oscillatory manner and are normally inhibited by inhibitory neurons.

The thousands of synapses for each neuron are in a continual state of flux, being modified during wakefulness with functions of consciousness and as new memories are being formed, during sleep as dreaming occurs and memories are being consolidated, and at all times as the functions of homeostasis are being performed and updated.

Dendritic spine ‘twitching’ predicted by Francis Crick

Fast twitching movement of the dendritic spine was predicted by Francis Crick (1982). Spontaneous calcium transients are associated with rapid contraction of the spine head. The twitching lasts from a few hundreds of a millisecond up to 2 s. At the end of the calcium flow, the spine relaxes to its original shape.

(Shepherd, Synaptic Organization of the Brain; Douglas; Neocortex, 497)

Neuron Functionality

Action potential is generated in the initial part of the axon where it connects with the cell body. (LeDoux; Synaptic Self, 47)

Nerve cells constantly maintain an electrical charge gradient. Keeping up this polarity takes energy created from oxygen metabolism. (Horstman; Healthy Aging Brain, 200)

Projection neurons tend to be idle in the absence of inputs. Inhibitory interneurons are often active all the time. (LeDoux; Synaptic Self, 50)

Glutamate is a ubiquitous excitatory transmitter in the brain. (LeDoux; Synaptic Self, 53)

GABA (an amino acid) is a neurotransmitter of inhibitory neurons. (LeDoux; Synaptic Self, 53)

Two major neurotransmitters: glutamate and GABA; released from different presynaptic neurons, bind to distinct postsynaptic receptors; glutamate excitatory, GABA inhibitory. (LeDoux; Synaptic Self, 54)

Glutamate and GABA are fast-acting; they cause an electrical change in the postsynaptic cell within milliseconds of being released from the presynaptic terminal, and their effect is over in a matter of milliseconds. (LeDoux; Synaptic Self, 57)

Neurotransmitters acting as modulators have slower and longer-lasting effects. (LeDoux; Synaptic Self, 57)

Rate at which a cell fires spontaneously is a function of certain electrical and chemical characteristics of the cell. (LeDoux; Synaptic Self, 64)

Cell's intrinsic properties, which may have a strong genetic component, will greatly influence everything a cell does. (LeDoux; Synaptic Self, 64)

Synapses are ultimately the key to the brain's many functions, and thus to the self. (LeDoux; Synaptic Self, 64)

In the cortex, roughly 65% of all cells are pyramidal cells that send their output to distant cortical areas, as well as locally via their axon collaterals. (Koch, Neuronal Theories; Mumford; Neuronal Architectures, 135)

Synapses

Thoughts Mediated as Synapse Connections

Thoughts are mediated as subsets of active signals via synapse connections. Synapses provide network connections between neurons, although only a small portion of the synapses are actively carrying signals at any one moment. Blood flow to the brain bringing glucose and oxygen to the mitochondria within neurons provides energy to operate the neuron spikes and the intricate biochemistry of neurotransmitters in the synapses. Signals on synapse connections are fleeting; they often persist no more than a millisecond or so. A varying subset of active synapse connections in the neural network forms the Dynamic Core, which is the Neural Correlate of Consciousness.

Research Study — Synapse Diagram

Research Study — Language—Associated Gene SRPX2 Regulates Synapse Formation

Research Study — Synapse Elimination via Astrocytes

Research Study — Synaptic Architecture 3D Model

Research Study — Synaptic Vesicles Molecular Machines

Dynamic Core mediates a mental pattern of thought at any one instant

The dynamic core is the instantaneous neural subnetwork that mediates a thought pattern, typically during the waking state. Many types of neurons in the brain can form a part of the Dynamic Core. Typical neurons can have thousands of dendrites receiving inputs from other neurons. These communications between neurons are in pulses, lasting a couple of milliseconds. Some pulses and receptors are excitatory, some are inhibitory. For a neuron to fire, the proper sequence and summation of input pulses must appear at the axon hillock. (Crick; Astonishing Hypothesis, 92, 93) (Calvin; Neil's Brain, 105, 107)

Enormous variation at the levels of neuronal chemistry, network structure, synaptic strength, temporal properties, memories, and motivational patterns governed by value systems. (Edelman; Wider than the Sky, 34)

Synapse Locations on Dendrites, Neuron Soma, Axon Terminals

Some synaptic terminals are located on dendrites, others on axon terminals, and still others on soma of the postsynaptic cell. (Kandel; Search of Memory, 335)

Location of synapses on the neuronal surface critically affects the function of the cell. (Kandel; Search of Memory, 335)

Research study — Learning and Memory in Pyramidal Neuron Dendrites

Synapses Habituate when Stimulated Repeatedly

When a synapse is stimulated repeatedly, it habituates; the number of quanta of neurotransmitter released decreases. Entry of calcium into the nerve terminal may regulate the efficiency of the synapse by increasing the probability of the release of neurotransmitter. Desensitization. (Changeux; Neuronal Man, 142-143)

Neurotransmitters and Their Receptors

Neurotransmitters and their receptors provide the functionality in synapses connecting neurons. Glutamate and GABA mediate the fast transmission of a few milliseconds, while a number of modulatory neurotransmitters affect the synaptic efficacy over a period of seconds, minutes, or hours. Glutamate is a neurotransmitter in projection neurons, while GABA is the principal neurotransmitter in interneurons.

Excitatory and Inhibitory Synapses

Inhibitory synapses oppose excitatory synapses. Inhibitory typically have a pore that doesn't pass sodium ions, just potassium or chloride ions, resulting in a potential that opposes the excitatory. About 40% of a neuron's inputs are inhibitory. It's all a balancing act between excitatory and inhibitory. (Calvin; Neil's Brain, 106)

Temporal Summation and Spatial Summation

Temporal summation and spatial summation of neuron inputs. (Calvin; Neil's Brain, 105)

Spikes, all-or-none (Quest 35) (Neuroscience 31, 47, 165)

1-10 mm/ms (Koch; Quest for Consciousness, 35)

Many types of neurons in the nervous system are endowed with particular types of intrinsic electrical activity. (Llinás; I of the Vortex, 9)

More than a dozen types of pores into neurons. (Calvin; Neil's Brain, 107)

Neurons are coincidence detectors and are superbly sensitive to signal correlations.

Intracellular calcium sensors regulate neurotransmitter release

Neurons communicate with each other through synaptic junctions. In the presynaptic neuron, voltage-gated calcium channels are activated in response to an action potential, allowing the entry of extracellular calcium. This triggers the fusion of neurotransmitter-laden semantic vesicles with the plasma membrane and the release of neurotransmitter molecules. (Nature, 29 Nov 2007, p. 623)

Long Term Potentiation (LTP)

Synapses show numerous forms of memory of their activation history. (Andersen; Hippocampus Book, 210)

Following a burst of impulses, any pulse in the next minute or so may release more than the standard amount of neurotransmitter. When longer times and more impulses are involved, it can lead to Long Term Potentiation (LTP). (Calvin; Neil's Brain, 108)

The functionality of synapses between neurons can change as a function of use. The more a synapse at a dendrite is used, the more effective it will be for future signals. Inversely, if a synapse is used rarely, it becomes less effective and may disappear. In this way, the synapses provide memory and learning for the neural network.

NMDA Receptors

NMDA receptor biochemical reactions are important for triggering signal transduction pathways that contribute to certain long-lasting modifications in the synapse that are important for learning and memory. (Kandel; Principles of Neural Science, 213)

Because NMDA receptors require a significant level of presynaptic activity before they can function maximally, long-term synaptic modifications mediated by the NMDA receptor is often referred to as activity-dependent synaptic modification. (Kandel; Principles of Neural Science, 213)

Blockade of the NMDA receptors produces symptoms that resemble the hallucinations associated with schizophrenia. (Kandel; Principles of Neural Science, 213)

Most excitatory hippocampus synapses are mediated by AMPA and NMDA receptors, which have strikingly different biophysical and pharmacological properties. (Andersen; Hippocampus Book, 213)

Whereas the number of NMDA receptors is relatively invariant, a tremendous range exists in the number of AMPA receptors at individual synapses. (Andersen; Hippocampus Book, 137)

AMPA receptors show a rapid rise time (100-600 µs at physiological temperature). This reflects both very fast binding kinetics and a high opening probability. (Andersen; Hippocampus Book, 213)

NMDA receptors have very slow kinetics and can continue to mediate an ion flux for several hundreds of milliseconds after the glutamate pulse has terminated (activation time constant is approximately 7 ms; deactivation time constants are approximately 200 ms and 1-3 seconds). (Andersen; Hippocampus Book, 215)

It is accepted that Ca2+ entry directly through the NMDAR channel is a trigger for NMDAR-dependent LTP. (Andersen; Hippocampus Book, 359)

Transmitter Gated channels

Transmitter gated channels produce the fastest and briefest type of synaptic action, lasting only a few milliseconds, on average. (Kandel; Principles of Neural Science, 250)

Longer-lasting effects

Longer-lasting effects of transmitters are mediated by activation of the G protein-coupled receptors and the receptor tyrosine kinases. (Kandel; Principles of Neural Science, 251)

Second Messenger actions

Many second messenger actions depend on activation of protein kinases, leading to phosphorylation of a variety of cellular proteins, including ion channels, which changes their functional state. (Kandel; Principles of Neural Science, 251)

Second messenger actions generally last from seconds to minutes. (Kandel; Principles of Neural Science, 251)

Second messenger actions do not mediate rapid behaviors but rather serve to modulate the strength and efficacy of fast synaptic transmission -- by modulating: (1) transmitter release, (2) sensitivity of ionotropic receptors, or (3) electrical excitability of the postsynaptic cell. (Kandel; Principles of Neural Science, 251)

Second messenger actions are implicated in emotional states, mood, arousal, and certain forms of learning and memory. (Kandel; Principles of Neural Science, 251)

Longest Lasting changes

Longest lasting changes in synaptic transmission involve changes in gene transcription, changes that can persist for days or weeks. (Kandel; Principles of Neural Science, 251)

The more permanent synaptic changes are thought to involve many of the same types of receptors and second messenger pathways involved in the shorter term modulatory actions. However, they may require repeated stimulation and more prolonged action of the second messengers. (Kandel; Principles of Neural Science, 251)

Synaptically induced activation of gene expression is critical for the storage of long-term memory. (Kandel; Principles of Neural Science, 251)

Research study — Synaptic Remodeling, and Network Activity

Research study — Synapses Pruned by Microglia

The results of a research study support the hypothesis that plasticity changes in synapses during waketime lead to a net increase in synaptic strength in many brain circuits and that sleep is required for synaptic renormalization.

Research study — Sleep and Synaptic Homeostasis

Link to — Consciousness Subject Outline