Evolution of Evolution of Complex Complex SystemsSystems

Lecture 5: Organism and nervous Lecture 5: Organism and nervous systemsystem

Peter Andras / Bruce CharltonPeter Andras / Bruce Charlton

peter.andras@ncl.ac.ukpeter.andras@ncl.ac.uk

bruce.charlton@ncl.ac.ukbruce.charlton@ncl.ac.uk

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ObjectivesObjectives Multi-cellular systemsMulti-cellular systems Tissues and organsTissues and organs Subsystems of organismsSubsystems of organisms Memory in the organismMemory in the organism Organism identityOrganism identity Nervous system: the information Nervous system: the information

subsystem of the organismsubsystem of the organism Adaptation in response to identity Adaptation in response to identity

violationsviolations Complexity of organismsComplexity of organisms

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The cell systemThe cell system

Protein – protein and protein – Protein – protein and protein – metabolite interactionsmetabolite interactions

Language: spatio-temporal pattern Language: spatio-temporal pattern of such interactionsof such interactions

Information subsystem: genomeInformation subsystem: genome

(www.cellsalive.com)

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The cell system from the The cell system from the outsideoutside

Communication unitCommunication unit Communication signals / Communication signals /

behaviours:behaviours: Expression of a set of proteins in the Expression of a set of proteins in the

cell membranecell membrane Release of proteins and other Release of proteins and other

metabolites as secretionsmetabolites as secretions Cell actionsCell actions

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Communication signals Communication signals between cellsbetween cells

Two cells, both cells communicate by Two cells, both cells communicate by expression and release of moleculesexpression and release of molecules

The communication signals are sent by one The communication signals are sent by one cell, transmitted to the other cell by cell, transmitted to the other cell by diffusion of released molecules or by diffusion of released molecules or by binding of surface molecules, and received binding of surface molecules, and received by the other cell through its receptor by the other cell through its receptor moleculesmolecules

E.g., neurons: neurotransmitters, electric E.g., neurons: neurotransmitters, electric junction moleculesjunction molecules

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Communication of cellsCommunication of cells Cells produce a sequence Cells produce a sequence

/ pattern of signals/ pattern of signals A new signal is A new signal is

determined by the determined by the current signals and the current signals and the signals of other cells signals of other cells received by the cellreceived by the cell

Note: we ignore the Note: we ignore the internal part of the cell, internal part of the cell, which actually which actually determines the signals determines the signals produced by the cellproduced by the cell

(cellbio.utmb.edu/cellbio)

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Rules of cell Rules of cell communicationscommunications

It is not possible to produce any signal after It is not possible to produce any signal after any other signalany other signal

The possible following signals are The possible following signals are determined by the interior mechanisms of determined by the interior mechanisms of the cellthe cell

From outside we see a conditional From outside we see a conditional probability distribution over the set of all probability distribution over the set of all communication signals that can be communication signals that can be produced by the cellproduced by the cell

E.g., refractory period in neurons that follow E.g., refractory period in neurons that follow spikesspikes

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Referencing in cell Referencing in cell communicationscommunications

The new communication depends The new communication depends on earlier communications of the on earlier communications of the cell and communications of other cell and communications of other cells, which are received by the cells, which are received by the cellcell

E.g., neurons: inhibition and E.g., neurons: inhibition and excitation signals received from excitation signals received from other cellsother cells

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Multi-cellular systemsMulti-cellular systems

Many cells which act as Many cells which act as communication unitscommunication units

Generate a system of Generate a system of communications communications between cells = between cells = organismorganism

E.g., bacteria biofilms, E.g., bacteria biofilms, slime mould, sponges, slime mould, sponges, cat, humancat, human

(www.shef.ac.uk/ ~mb1rwa/rwaresea.html)

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Simple multi-cellular Simple multi-cellular systemssystems

Hydra: inner wall, outer wall, Hydra: inner wall, outer wall, tentacles, foottentacles, foot

Behaviour: filter feedingBehaviour: filter feeding

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The environment of the The environment of the organismorganism

Anything that is not part of the inter-Anything that is not part of the inter-cellular communication system is part cellular communication system is part of the environmentof the environment

Communications with other cells, e.g., Communications with other cells, e.g., digestive bacteriadigestive bacteria

The boundary is a communicational The boundary is a communicational boundaryboundary

Usually the boundary is well-defined as Usually the boundary is well-defined as skin in higher animalsskin in higher animals

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Actions of organismsActions of organisms

Action: a pattern of inter-cellular Action: a pattern of inter-cellular communicationscommunications

E.g., extending a tentacle of a hydraE.g., extending a tentacle of a hydra The actions act upon the environmentThe actions act upon the environment The communications leading to The communications leading to

actions are referenced by other inter-actions are referenced by other inter-cellular communicationscellular communications

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Perceptions of organismsPerceptions of organisms

The environment influences the The environment influences the behaviour of cells and so modifies behaviour of cells and so modifies the conditional probability the conditional probability distributions of cell communicationsdistributions of cell communications

E.g., a food particle triggers the E.g., a food particle triggers the release of digestive enzymes and release of digestive enzymes and the digestion of the food particle by the digestion of the food particle by the hydrathe hydra

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Specialized cellsSpecialized cells Some communication units (cells) may Some communication units (cells) may

specialize to produce a limited set of possible specialize to produce a limited set of possible communication signalscommunication signals

The specialization means the change of the The specialization means the change of the conditional distributions of continuation conditional distributions of continuation signals, i.e., sharpening the distributionsignals, i.e., sharpening the distribution

Specialization happens by selection of a part of Specialization happens by selection of a part of the genome to be regularly expressed in the the genome to be regularly expressed in the cellcell

Specialization = constraints on inter-cellular Specialization = constraints on inter-cellular communications communications structure structure

E.g., stem cells – generalist cells; muscle cells E.g., stem cells – generalist cells; muscle cells – specialist cells– specialist cells

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TissuesTissues

Specialized cells form Specialized cells form tissuestissues

Tissues usually have a Tissues usually have a special function within the special function within the organism, i.e., they deal organism, i.e., they deal with a subset of actions with a subset of actions produced by the organismproduced by the organism

E.g., muscle, bone, neural E.g., muscle, bone, neural tissuetissue

(www.ucd.ie/vetanat/calnet/muscle)

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Tissue subsystemsTissue subsystems

Tissues are formed by specialized cells, Tissues are formed by specialized cells, which produce preferentially a subset of which produce preferentially a subset of possible inter-cellular communications – possible inter-cellular communications – structure constraintsstructure constraints

These specific communications define These specific communications define the tissue communication systemthe tissue communication system

E.g., muscle cells communicate with E.g., muscle cells communicate with each other about stretching and each other about stretching and contractingcontracting

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Tissue languageTissue language

The language of a tissue system is a specialized The language of a tissue system is a specialized / modified subset of the organism’s language:/ modified subset of the organism’s language: The set of conditional probabilities determining which The set of conditional probabilities determining which

signal follows other signalssignal follows other signals The conditional probabilities are sharpened to limit The conditional probabilities are sharpened to limit

the communications to the tissue specific the communications to the tissue specific communicationscommunications

E.g., muscles: all inter-muscle cell E.g., muscles: all inter-muscle cell communications are about communications are about stretching/contractingstretching/contracting

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The environment of The environment of tissuestissues

Communication boundary: cells Communication boundary: cells within a tissue communicate within a tissue communicate frequently, relatively rare frequently, relatively rare communications with non-tissue communications with non-tissue cellscells

The boundary is within the The boundary is within the organism’s system boundaryorganism’s system boundary

E.g., nerves and musclesE.g., nerves and muscles

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The function of organisms and The function of organisms and tissuestissues

Self-reproduction and expansion of Self-reproduction and expansion of their own communication systemtheir own communication system

The self-reproduction and expansion The self-reproduction and expansion of the organism limits the self-of the organism limits the self-expansion and reproduction of it’s expansion and reproduction of it’s sub-systems (tissues)sub-systems (tissues)

Implication: size, shape, Implication: size, shape, organisation, location of tissues organisation, location of tissues within the organismwithin the organism

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Programmed cell deathProgrammed cell death

Organismal communications limit the Organismal communications limit the growth of tissuesgrowth of tissues

This happens by inducing tissue shaping This happens by inducing tissue shaping by programmed cell deathby programmed cell death

Programmed cell death is the result and Programmed cell death is the result and mean of limiting tissue specific mean of limiting tissue specific communications as part of the communications as part of the expansion of the organism’s expansion of the organism’s communicationscommunications

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CancerCancer

Cancerous cells loose their ability to Cancerous cells loose their ability to participate in the tissue and organism participate in the tissue and organism communicationscommunications

They become communication units that They become communication units that communicate mainly between communicate mainly between themselves, and reduce their themselves, and reduce their communications with the rest of the communications with the rest of the organismorganism

The cancer is as independent multi-The cancer is as independent multi-cellular system that expands disregarding cellular system that expands disregarding the overall expansion of the organismthe overall expansion of the organism

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Organs of organismsOrgans of organisms

Organs: specialized parts of an Organs: specialized parts of an organism performing some special organism performing some special organism behaviourorganism behaviour

E.g., tentacles of a hydra, ear of a E.g., tentacles of a hydra, ear of a cat, hand of a humancat, hand of a human

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Are the organs systems ?Are the organs systems ? Consider the cells and tissues Consider the cells and tissues

composing an organ: e.g., ear of a catcomposing an organ: e.g., ear of a cat The co-localisation of cells implies The co-localisation of cells implies

relatively frequent communications relatively frequent communications between neighbouring cellsbetween neighbouring cells

At the same time: usually there is also a At the same time: usually there is also a considerable amount of communication considerable amount of communication between organ located and non-organ between organ located and non-organ located cells (e.g., blood, neurons, located cells (e.g., blood, neurons, lymphatic cells)lymphatic cells)

Organs are not always systemsOrgans are not always systems

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Component ‘systems’ of Component ‘systems’ of organismsorganisms

Usually the organism is composed Usually the organism is composed of several functional ‘systems’of several functional ‘systems’

E.g., digestive system, locomotor E.g., digestive system, locomotor system, circulatory system, system, circulatory system, respiratory systemrespiratory system

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What are the functional What are the functional ‘systems’ ?‘systems’ ?

They contain cells belonging to several They contain cells belonging to several tissuestissues

The co-location implies some level of The co-location implies some level of dense inter-neighbour communicationsdense inter-neighbour communications

There is also a significant amount of There is also a significant amount of communication with non-local cellscommunication with non-local cells

Like organs the functional ‘systems’ of Like organs the functional ‘systems’ of an organism are communication an organism are communication patterns of cells and tissues composing patterns of cells and tissues composing the organismthe organism

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Physiological diseasesPhysiological diseases

Disease: local disturbance of inter-Disease: local disturbance of inter-cellular communications (e.g., cellular communications (e.g., bacteria produce toxins that bacteria produce toxins that change cell communications)change cell communications)

The tissues of the involved cells do The tissues of the involved cells do not function normally, i.e., the not function normally, i.e., the tissue specific communication do tissue specific communication do not follow their regular patternnot follow their regular pattern

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Meaningful communications - Meaningful communications - OrganismOrganism

All inter-cellular communications that All inter-cellular communications that refer to other such communications refer to other such communications and provide reference for further and provide reference for further such communicationssuch communications

Such inter-cellular communications Such inter-cellular communications contribute to the self-reproduction contribute to the self-reproduction and expansion of the organism and expansion of the organism systemsystem

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Meaningful communications - Meaningful communications - TissuesTissues

All inter-cellular communications All inter-cellular communications that follow the sharpened / that follow the sharpened / constrained continuation rules of constrained continuation rules of the tissue grammarthe tissue grammar

The contribute to the reproduction The contribute to the reproduction and extension of the tissueand extension of the tissue

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Meaningless communications Meaningless communications - Tissues- Tissues

Inter-cellular communications Inter-cellular communications between tissue cells that do not between tissue cells that do not follow the grammar of the tissue follow the grammar of the tissue language, which cannot become the language, which cannot become the reference for further tissue system reference for further tissue system regenerating and expanding regenerating and expanding communicationscommunications

E.g., cancer cells or degenerated E.g., cancer cells or degenerated muscle cellsmuscle cells

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Meaningless communications Meaningless communications - Organism- Organism

Inter-cellular communications that Inter-cellular communications that do not respect the language of the do not respect the language of the organismorganism

Faulty communicationsFaulty communications E.g., diseased cells and tissuesE.g., diseased cells and tissues

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Memory of the organism Memory of the organism systemsystem

Collecting information about the cell-Collecting information about the cell-communications composing the organismcommunications composing the organism

Analysing perceptions, modelling and Analysing perceptions, modelling and controlling the actionscontrolling the actions

Such memories facilitate the Such memories facilitate the reproduction of system communicationsreproduction of system communications

Monitoring of inter-cellular Monitoring of inter-cellular communications is done by immune cells communications is done by immune cells and neuronsand neurons

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Immune cellsImmune cells

Immune cells monitor the validity of Immune cells monitor the validity of organismal communications and organismal communications and detect wrong communications – e.g. detect wrong communications – e.g. diseased cellsdiseased cells

Immune cells define the identity of Immune cells define the identity of the organism system and enforce it the organism system and enforce it by trying to eliminate cells that do not by trying to eliminate cells that do not fit the rules of organism fit the rules of organism communicationscommunications

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NeuronsNeurons

Neurons monitor inter-cellular Neurons monitor inter-cellular communications and facilitate the communications and facilitate the recreation of system conform recreation of system conform communications – e.g. movements communications – e.g. movements of the organismof the organism

Communications between neurons Communications between neurons combine memories of organism combine memories of organism communicationscommunications

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Information subsystemInformation subsystem The immune system constitutes a The immune system constitutes a

component of the information system of the component of the information system of the organism dealing with identity checking and organism dealing with identity checking and identity enforcement of the organismidentity enforcement of the organism

The main part of the information subsystem The main part of the information subsystem of the multi-cellular organism is its nervous of the multi-cellular organism is its nervous system that processes memory system that processes memory communications and contributes to large communications and contributes to large extent to the identity definition, checking extent to the identity definition, checking and enforcement communications within the and enforcement communications within the organism organism

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The nervous systemThe nervous system

Hydra: neurons dispersed in the body Hydra: neurons dispersed in the body dealing with local action and perception; dealing with local action and perception; they are loosely connected and their inter-they are loosely connected and their inter-neuron communications are not much more neuron communications are not much more than their communications with other non-than their communications with other non-neuron cells; they do not form a nervous neuron cells; they do not form a nervous tissuetissue

Higher organism: there is a nervous tissue Higher organism: there is a nervous tissue with intense communications within the with intense communications within the tissue, e.g., insect ganglions, human braintissue, e.g., insect ganglions, human brain

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Communications between Communications between neuronsneurons

Signals: transmitter molecules, Signals: transmitter molecules, electric junction molecules – inter-electric junction molecules – inter-cellular interactionscellular interactions

Integration of incoming signals Integration of incoming signals followed by the generation of followed by the generation of outgoing signaloutgoing signal

Signalling actions: graded Signalling actions: graded potentials or spikespotentials or spikes

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Referencing in neuron Referencing in neuron communicationscommunications

The incoming spatio-temporal The incoming spatio-temporal pattern of neural signals pattern of neural signals determines the outgoing signaldetermines the outgoing signal

E.g., IF (integrate-and-fire) neuronsE.g., IF (integrate-and-fire) neurons

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Nervous system and its Nervous system and its environmentenvironment

System: communications between System: communications between neuronsneurons

Dense communications between Dense communications between neurons, relatively rare neurons, relatively rare communications with other cellscommunications with other cells

Dense / rare communications Dense / rare communications boundary of the system / boundary of the system / environmentenvironment

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Actions of the nervous Actions of the nervous systemsystem

Neurons send signals to muscles and Neurons send signals to muscles and other cells triggering communications other cells triggering communications in their local tissue systemsin their local tissue systems

These are actions of the nervous These are actions of the nervous system on it’s environmentsystem on it’s environment

Such actions may result in actions of Such actions may result in actions of the organism on it’s environmentthe organism on it’s environment

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Perceptions of the nervous Perceptions of the nervous systemsystem

As a result of nervous system actions and As a result of nervous system actions and organism actions the environment acts organism actions the environment acts upon the organism and its tissues, upon the organism and its tissues, modifying the local communications modifying the local communications between cellsbetween cells

These local communications are received These local communications are received by neurons and specialized receptor cellsby neurons and specialized receptor cells

The effects of these communications The effects of these communications generate changed communications within generate changed communications within the nervous system implying perceptions the nervous system implying perceptions within the nervous systemwithin the nervous system

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Language of the nervous Language of the nervous systemsystem

Spatio-temporal patterns of neural Spatio-temporal patterns of neural signals and conditional signals and conditional continuation distributions continuation distributions

Referencing rules and continuation Referencing rules and continuation rulesrules

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Meaningful neural Meaningful neural communicationscommunications

Communications that follow the Communications that follow the rules of the grammar, reference rules of the grammar, reference other communications, and are other communications, and are referenced by further referenced by further communicationscommunications

Contribute to the reproduction and Contribute to the reproduction and extension of the nervous systemextension of the nervous system

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Meaningless neural Meaningless neural communicationscommunications

False perceptions, false action commandsFalse perceptions, false action commands Lead to model errors, wrong behaviours – Lead to model errors, wrong behaviours –

faulty communications leading to errorsfaulty communications leading to errors E.g., epileptic seizure = short term self-E.g., epileptic seizure = short term self-

reproducing and expanding reproducing and expanding communication system involving neurons communication system involving neurons as communication units that does not fit as communication units that does not fit into the communication system of the into the communication system of the nervous systemnervous system

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Subsystems of the nervous Subsystems of the nervous systemsystem

Constraints on communication - Constraints on communication - structuresstructures

Neural communications about Neural communications about some particular subset of actions some particular subset of actions and / or perceptions – constrained and / or perceptions – constrained communicationscommunications

E.g., motor system, visual system, E.g., motor system, visual system, olfactory systemolfactory system

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Reproduction and expansion Reproduction and expansion of the nervous systemof the nervous system

Neurons which do not receive and Neurons which do not receive and send meaningful signals diesend meaningful signals die

New communications referencing New communications referencing earlier ones and providing earlier ones and providing reference for further more inter-reference for further more inter-neuron communicationsneuron communications

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Identity violationsIdentity violations

Faults: wrong inter-cellular Faults: wrong inter-cellular communications – e.g. cancer, phantom communications – e.g. cancer, phantom painpain

Errors: lack of continuation of Errors: lack of continuation of communications – e.g. toxins blocking communications – e.g. toxins blocking channels in neuromuscular junctions, channels in neuromuscular junctions, asphyxiation – lungs cannot exchange CO2 asphyxiation – lungs cannot exchange CO2 for oxygenfor oxygen

Failure: neuro-degenerative disease, Failure: neuro-degenerative disease, infection leading to death of the organisminfection leading to death of the organism

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Adaptation – Organism Adaptation – Organism Lack of food triggers the movement of C. Lack of food triggers the movement of C.

Elegans worms:Elegans worms: There is an expectation of inter-cellular There is an expectation of inter-cellular

communications, which can happen only if communications, which can happen only if there is enough nutrient in the body of the there is enough nutrient in the body of the wormworm

Lack of food causes the lack of continuation of Lack of food causes the lack of continuation of the above inter-cellular communicationsthe above inter-cellular communications

This is monitored by the nervous system, which This is monitored by the nervous system, which sends new communications to the muscle cells sends new communications to the muscle cells triggering the movement of the worm towards triggering the movement of the worm towards a place with possibly more bacterial fooda place with possibly more bacterial food

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Adaptation – Nervous Adaptation – Nervous systemsystem

New connections between neurons New connections between neurons are formed and many other existing are formed and many other existing connections released during the connections released during the development of the organismdevelopment of the organism

E.g. lack of visual input may lead to E.g. lack of visual input may lead to the participation of normally vision the participation of normally vision brain areas in the processing of brain areas in the processing of auditory information in young catsauditory information in young cats

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Complexity of the nervous Complexity of the nervous systemsystem

Amount of communications and Amount of communications and neuronsneurons

Number of sub-systemsNumber of sub-systems More complex information system More complex information system

allows more complex description of allows more complex description of the organism / environment the organism / environment allowing more efficient allowing more efficient maintenance and reproduction of maintenance and reproduction of the organismthe organism

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Complexity of organismsComplexity of organisms

No nervous system / information No nervous system / information subsystem subsystem low complexity low complexity

Complex nervous system Complex nervous system high high complexitycomplexity

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Summary – 1 Summary – 1

Multi-cellular systemsMulti-cellular systems TissuesTissues OrgansOrgans Functional ‘systems’Functional ‘systems’ MemoryMemory IdentityIdentity

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Summary – 2 Summary – 2

Organism information subsystem: Organism information subsystem: nervous systemnervous system

The system of neuronsThe system of neurons Subsystems of the nervous systemSubsystems of the nervous system Complexity Complexity

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Q&A – 1 Q&A – 1

1.1. Is it true that cells communicate with each Is it true that cells communicate with each other by generating lipid membranes ?other by generating lipid membranes ?

2.2. Is it true that referencing in a multi-cellular Is it true that referencing in a multi-cellular system means that each cell’s system means that each cell’s communication depends on its earlier communication depends on its earlier communication signals and the communication signals and the communication signals of other cells ?communication signals of other cells ?

3.3. Is it true that the letters of the neural Is it true that the letters of the neural communication language in higher nervous communication language in higher nervous systems are the spikes, while the words of systems are the spikes, while the words of the communications are spatio-temporal the communications are spatio-temporal patterns of spikes ?patterns of spikes ?

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Q&A – 2 Q&A – 2

4. Is it true that the muscle cells form a tissue 4. Is it true that the muscle cells form a tissue system, which is a subsystem of the organism system, which is a subsystem of the organism ??

5. Is it true that the environment for the muscle 5. Is it true that the environment for the muscle tissue is the same as the environment for the tissue is the same as the environment for the whole organism ?whole organism ?

6. Is it true that the programmed cell death 6. Is it true that the programmed cell death causes meaningless communications within a causes meaningless communications within a tissue ? What about this in the context of a tissue ? What about this in the context of a cell system ?cell system ?

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Q&A – 3 Q&A – 3

7. Is it true that organs constitute 7. Is it true that organs constitute subsystems of an organism ?subsystems of an organism ?

8. Is it true that physiological diseases can 8. Is it true that physiological diseases can be seen as generation of meaningless be seen as generation of meaningless communications within some local communications within some local tissue ?tissue ?

9. Is it true that the perceptions of the 9. Is it true that the perceptions of the nervous system are about the nervous system are about the environment of the organism ?environment of the organism ?

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Q&A – 4 Q&A – 4

10. Is it true that nervous system 10. Is it true that nervous system describes the environment of the describes the environment of the organism ?organism ?

11. Is it true that the nervous system has 11. Is it true that the nervous system has subsystems ?subsystems ?

12. Is it true that organisms without 12. Is it true that organisms without nervous system can have the same nervous system can have the same complexity as organisms with nervous complexity as organisms with nervous system ?system ?