The Architecture of Nervous Systems

The Architecture of Nervous Systems

General principles from an evolutionary perspective.

Development of the vertebrate nervous system

Identity and organization of functional systems

Some basic structural features of the nervous system.

Mary Kate Worden, Ph.D. Dept of Neuroscience ([email protected])

The Architecture of Nervous Systems

General principles from an evolutionary perspective.

Development of the vertebrate nervous system

Identity and organization of functional systems

Some basic structural features of the nervous system.

And:

Non-mammalian neurobiology.

Mary Kate Worden, Ph.D. Dept of Neuroscience ([email protected])

Cnidaria: hydra (also jellyfish, corals, and anemones)

Nerve net: diffusely distributed network of neurons

Two layers of body wall

Hydra

spongesHydra

Sensory cells are bipolar

Effector cells are muscles or glands

Motorneurons signal to effector cells and to each other as well.

Some general features of the nervous system are present in primitive animals.

Fundamental features of nervous systems:

Polarity of signaling:

information flows from dendrites and soma to axon

(exception: amacrine processes)

Divergence of signaling:

information travels widely

Convergence of signaling:

any one neuron receives input from multiple sources.

Cephalization:

neurons and sensory receptors become concentrated rostrally

Centralization:

neurons concentrate in body areas with specialized function

Flatworms: planaria

Flatworms are bilaterally symmetric and have three tissue layers (ectoderm, mesoderm and endoderm)

The nervous system has collections of neurons called ganglia. Axons run through nerve cords.

Interneurons:

local interneurons

projection interneurons

Increase possibilities for information processing. Also can act as switches, pacemakers.

Flatworms: planaria

Annelids and arthropods (and molluscs):

are segmented: body segments are repeated along the rostrocaudal axis

have a ventral nerve cord

bilateral ganglia or fused ganglia are present in each segment and are connected by longitudinal bundles of axons

Examples:

Molluscs:

The Nobel Prize in Physiology or Medicine for 2000

Arvid Carlsson, Paul Greengard and Eric Kandelfor their discoveries concerning "signal transduction in the nervous system"

-are individually identifiable, have the same morphology in each individual

-can be repeatedly located in the same position

-are often very large in size

Invertebrate neurons: the Retzius cells of the leech as an example

In a ganglion in a test tube

Blackshaw et al. Journal of Anatomy 204:13-24 (2004) Identifying genes for neuron survival and axon outgrowth in Hirudo medicinalis

Amphioxus: a primitive chordate

The amphioxus has a dorsal nerve cord and a notochord.

Amphioxus: a primitive chordate

The amphioxus has a dorsal nerve cord and a notochord.

Vertebrates: the nervous system forms from the neural plate.

Telencephalon

Diencephalon

Mesencephalon

Metencephalon

Myelencephalon

Spinalcord

Descriptors for relationships:rostral (toward nose)caudal (toward tail)dorsal (toward back)ventral (toward belly)

superior (above)inferior (below)anterior (in front)posterior (behind)

Note: in the spinal cord dorsal/ventral and anterior/posterior are used interchangeably.

Vocabulary

Central nervous system: spinal cord and brain, including retina.areas containing nerve cell bodies = gray matterareas containing axons = white matterareas in which axons and dendrites synapse = neuropilcollections of nerve cell bodies= nuclei (nucleus)axon fiber tracts: fasciculi (fasciculus), peduncle,

commissure, lemnisci (lemniscus), tracts

Peripheral nervous system: sensory and autonomic ganglia, peripheral nerves.

collections of nerve cell bodies = gangliacollections of axons = nerves

Vocabulary

Afferents: axons (nerve fibers) projecting into CNS , inputs to brain, ascending fibers

(example: sensory fibers from periphery)

Efferents: fibers projecting out of CNS, outputs from brain; descending fibers

(example: motor fibers projecting to muscles.)

Interneurons: Intrinsic neurons with axonal connections that remain within the local circuit

Vocabulary

The spinal cord.

Cervical and lumbar enlargements: arise dueto masses of motoneurons for upper and lower limbs.

Central canal

Dorsal roots: carry sensory information from dorsal root ganglion into the dorsal horn.

Ventral roots: carry motor information out of the ventral horn.

The spinal cord.

Dorsal roots: carry sensory information from dorsal root ganglion into the dorsal horn.

Ventral roots: carry motor information out of the ventral horn.

The spinal cord.

Afferent

Efferent

Local circuits within the cortex also have afferents (inputs) and efferents (outputs).

Afferent Efferent

The Organization of the Nervous System

Neuroethology: the study of how nervous systems generate natural behaviour in animals.

"The intent is to bring together neuroscientists and ethologists to advance our understanding of the neural basis of behaviour in animals, whether they be vertebrates or invertebrates. There is an intrinsic interest in explaining the huge range of behaviour shown by many different sorts of animals, but also in exploiting this diversity to illuminate basic principals of the organisation and design of brains in general. A continuing driving force is therefore the expectation that the study of neural mechanisms underlying a specific behaviour in a particular animal will elucidate mechanisms that are more generally applicable. Thus the specializations of owls for hearing have given insights into how sounds can be localized, the relative simplicity of the spinal cord of lampreys has told us much about the connectivity and pharmacology of neurons involved in generating locomotion, and the detailed analysis of small networks in crabs, leeches and insects continually reveal unexpected mechanisms that must be incorporated into our thinking about the functioning of more complex brains."

http://www.neuroethology.org

The basic wiring diagram of the nervous system.

(everything is connected to everything)

Behavior is determined by the motor system, which is influence by sensory input, intrinsic behavioral state and cognition.

Reflexes result from sensory input, some inputs are voluntary.

History of neuroanatomical techniques:

1873: Golgi impregnation

1885: Selective stains for degenerating myelinated fibers (Marchi and Algeri)

Mid 1950s: selective silver staining for all fibers (Nauta)

1970s: antibody staining, fluorescent markers, radiolabelled amino acids, retrograde tracers, in situ hybridization of nucleic acids

The Nobel Prize in Physiology or Medicine 1906

Camillo Golgi Santiago Ramón y Cajal

Pavia University Pavia, Italy

Madrid University Madrid, Spain

"in recognition of their work on the structure of the nervous system"

Golgi staining: potassium chromate and silver nitrate (1873)

Golgi's drawing of the hippocampus impregnated by his stain (from Golgi's

Opera Omnia).

Nobel e-museum

Camillo Golgi Nobel Lecture December 11, 1906

The Neuron Doctrine- theory and facts. “..Far from being able to accept the idea of the individuality and independence of each nerve element, I have never had reason, up to now, to give up the concept which I have always stressed, that nerve cells, instead of working individually, act together, so that we must think that several groups of elements exercise a cumulative effect on the peripheral organs through whole bundles of fibers.”

The nervous system as a diffuse reticular syncytium?

(i.e. a mass of cytoplasm with many nuclei but no internal cell boundries)

The Neuron Doctrine: (Santiago Ramon y Cajal)

Neurons are cells. Each is an individual entity anatomically, embyologically, and functionally.

Also: Neurons have a functional polarity.

l

Neurons have a functional polarity.

Incoming information arrives

Information is assimilated

Information is sent to next neuron

synapses

The irresistible conception of the reticular suggestion of which I have spoken to you (which changes every 5 or 6 years) has led several physiologists and zoologists to object to the doctrine of propagation of nerve currents by contact or at a distance. All their allegations are based on the findings of incomplete methods... In spite of the pains I have taken to perceive the supposed intercellular anastomoses in preparations made with diverse coloration processes I have never succeeded in finding any definite ones, that is to say, showing themselves as clearly and sharply as the free endings. If the said intercellular unions are not the result of an illusion, they represent accidental dispositions, perhaps deformities whose value would be almost nil in the face of the nearly infinite quantity of the perfectly observed facts of free ending.

Santiago Ramon y Cajal

Nobel lecture, Dec 12, 1906

The structure and connexions of neurons.

Synapses visualized by electron microscopy.

(20 nm cleft with synaptic vesicles on one side and postsynaptic density on the other)

REVISIONS of the NEURON DOCTRINE 1. The presence of electrical synapses – gap junctions (Furshpan and Potter, 1959) 2. Axo-axonic synapses 3. Dendro-dendritic synapses (e.g. amacrine cells of the retina; granule cells of the olfactory bulb (Shepherd))

4. Transynaptic regulation of transmitters, enzymes; transynaptic transport of amino acids, viruses 5. Metabolic subunits within the neuron (e.g. spines as microcompartments) 6. Backpropogation of action potentials from the soma to the dendrites

Laslo Zaborsky, Ph.D. MD. Rutgers U.

Multipolar

Unipolar

J. Comp. Neurol. 462(2): 168-179

Example of morphology of an invertebrate neuron:

the parasol cell of the crayfish brain.

(Mike Mellon, UVA Dept of Biology)

Olfactory,photic, tactile

Examples of morphology of vertebrate neurons.

Motor neurons and interneurons typically unipolar

Neuronal somata in rind or ganglia

Dendritic processes arise directly from axons in most cases

Synapses in neuropil

Few types glia

Lack myelin

Large cells in many instances

Individually identifiable in many instances

Neural circuits have relatively few neurons

Motor neurons and interneuons typically multipolar

Neuronal somata typically grouped in nuclei, cortical lamina or throughout ganglia

Dendritic processes arise from soma

Several distinct types of glia

Have myelin and thus saltatory conduction

Few cells that are very large

Few individually identified neurons

Neural circuits have many components

Similarities and differences between the nervous systems of invertebrates and vertebrates

Inverebrate nervous systems Vertebrate nervous systems

Nature 417, 359 - 363 (16 May 2002)

Robots in invertebrate neuroscience

BARBARA WEBB • Can we now build artificial animals? A combination of robot technology and

neuroethological knowledge is enabling the development of realistic physical models of biological systems. And such systems are not only of interest to engineers. By exploring identified neural control circuits in the appropriate functional and environmental context, new insights are also provided to biologists.

Robot modeling of a cricket’s escape response.

Nature 417, 359 - 363 (16 May 2002)

Robots in invertebrate neuroscience

BARBARA WEBB

…invertebrate systems have been a particularly successful area for the approach. Invertebrate behaviours tend to be more stereotyped and thus easier to analyse comprehensively. The number of neural connections between sensing and action is orders of magnitude less than for vertebrates, making the possibility of complete pathway mapping plausible. We should have comparable processing power available in modern computers to that in insect brains, so failure to replicate their behavioural capabilities will indicate areas in which we lack knowledge of how the systems work.

Underwater walking

Joseph Ayers (2004)

Arthropod structure and development 33:347-360

insight overview318 NATURE | VOL 417 | 16 MAY 2002 | www.nature.com

Non-mammalian models for studyingneural development and functionEve Marder

Early neuroscientists scoured the animal kingdom for the ideal preparation with which to study specific problems of interest. Today, non-mammalian nervous systems continue to provide ideal platforms for the study of fundamental problems in neuroscience. Indeed, the peculiarities of body plan and nervous systems that have evolved to carry out precise tasks in unique ecological niches enable investigators not only to pose specific scientific questions, but also to uncover principles that are general to all nervous systems.

Nature 417, 364 - 365 (16 May 2002)

All Creatures Great and Small: National Institutes of Health

NINDS, NICHD, NIDA, NIDCD, NIGMS, NIMH : statements detailing the non-mammalian systems they fund and why.

http://www.nature.com/

Highlights:

A neural network where all the major elements (anatomy, transmitters, presynaptic firing patterns, postsynaptic physiology) are known.

A quantitative network model which can simulate all of the above.

A dataset of inputs and outputs recorded from a behaving animal.

A fundamental question in neuroscience:

How does the CNS elicit behavior in a changing environment?

Brezina V, Horn CC, Weiss KR (2005) J Neurophysiol. 2005 93(3):1523-56.

Modeling neuromuscular modulation in Aplysia. III. Interaction of central motor commands and peripheral modulatory state for optimal behavior.

.

Highlights:

A neural network where all the major elements (anatomy, transmitters, presynaptic firing patterns, postsynaptic physiology) are known.

A quantitative network model which can simulate all of the above.

A dataset of inputs and outputs recorded from a behaving animal.

A fundamental question in neuroscience:

How does the CNS elicit behavior in a changing environment?

Brezina V, Horn CC, Weiss KR (2005) J Neurophysiol. 2005 93(3):1523-56.

Modeling neuromuscular modulation in Aplysia. III. Interaction of central motor commands and peripheral modulatory state for optimal behavior.

.

Surprising results: The CNS is not the master, the periphery is semi-autonomous.

Random variability may be an optimal strategy in an uncertain environment.

Aplysia californica

simple nervous system (20,000 neurons)

Accessory radula closer (ARC): buccal muscle (feeding)

http://fulcrum.physbio.mssm.edu/~seaslug/Seaweed.html

Within the motor system M there are

central pattern generators (CPGs) and motorneurons.

Within the motor system M there are

central pattern generators (CPGs) and motorneurons.

Two motorneurons control the muscle.

Two motorneurons control the muscle.

NMT= neuromuscular transform

CPG

A CPG controls the motorneurons.

NMT= neuromuscular transform

Modeling the circuit:

Fire the motorneurons in patterns, simulate muscle response.

Add and subtract modulators, simulate muscle response

What if firing patterns are irregular?

Different components of the NMT have different time scales, there will be history-dependence to the output of the system.

Regular firing patterns of B15 and B16


Interruption of firing pattern:K decays, C does not, therefore S increases

Performance transiently reappears.


Modulatory state varies dynamically with the history of the system and alters subsequent performance by the same pattern.

Interruption of firing pattern:K decays, C does not, therefore S increases

Performance transiently reappears.

1. One modulator improves performance, the other reduces it.

2. Simultaneous release of both combine to optimize performance

3. Muscle performance is surprisingly good for irregular firing patterns.

BUT…..

What happens in the animal?

Summarizing………

Feeding

Irregular bursts of activity, variations in burst shapes over 749 cycles

f -instantaneous firing frequency

fB15, fB16

The CPG generates a new, essentially random combination of parameters in every cycle.

The CPG is the primary source of variability in the system.

Trial and error strategy? Is this the best strategy?







Test:

Using the model, compare performance in the 2.5 hour irregular meal with several regular patterns.

Summary

I: Peripheral modulation is essential for superior performance.

II: Components of the NMT interact in nonlinear, context and task-dependent combinations to guarantee robust overall performance over all the contexts and tasks that might arise.

III. Both the slow and fast dynamics of the modulatory state are important for performance.

IV. To what degree can the CNS predict and control motor performance?

Summary

I: Peripheral modulation is essential for superior performance.

II: Components of the NMT interact in nonlinear, context and task-dependent combinations to guarantee robust overall performance over all the contexts and tasks that might arise.

III. Both the slow and fast dynamics of the modulatory state are important for performance.

IV. To what degree can the CNS predict and control motor performance?

Accurate prediction and control of results of any one cycle is not critical.

CPG output is random: Prediction of peripheral result is not good.predicts fast basal contraction and Kslow effects not predicted (C and R)

The periphery has its own memory and acts semi-autonomously.

The network stabilizes overall performance over a variety of circumstances, rather than performance in any single cycle.

The CNS does not issue direct commands, it issues “suggestions”

BIG PICTURE

Firing properties of an interneuron.

Motor movement.

Behavior

Field potentials.

Motor movement/

Behavior

Crayfish tail flip

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The Architecture of Nervous Systems