Lecture 3: From Brain To Neuron

Front 1

From brain to neuron

Back 1

•Cerebrospinalfluid, blood vessels

•Braincells

•Introductionto neuronal signalling andelectricity

Front 2

Cerebrospinal fluid

Back 2

•Foundin ventricles, between meninges, and around brain cells

- CSFcirculates around brain – between the membranes(meninges) that surround the brain and along large blood vessels as well asthrough the ventricles.

-CSF also fills the smallextracellular space around neurons. Its makeup – the concentrations ofsubstances in it - controls theenvironment experienced by cells

- CSF cushions the brain from impactsto the

head, but also clears the brain of unwanted products such as broken downproteins. E.g. beta amyloid. Which isflushed out and cleared into blood vessels.

Front 3

Cerebrospinal fluid

Back 3

•Ventricles are fluid-filled spaces in the brain.

•CSF is produced from ependymal cells that line the ventricles

•Meningesare membranes surrounding the brain – dura (tough outer membrane), arachnoidand pia (next to brain surface)

Front 4

Blood Supply

Back 4

•Brainneeds lots of energy

•Thereforehas a specialisedblood supply

- Stroke:blocked cerebral blood vessels

- very important to keep blood flowto the brain

– fed by 4 main arteries: form a circle (circle of Willis) thatmeans that if one gets blocked others can compensate.

Front 5

Regulating blood supply

Back 5

- brain can finely regulate its blood supply

- means increase in regional brain activity

increases blood supply to that region.

- this increase in the blood supply is thebasis of the signal detected using functional MRI. So these studies don’t directly measureneuronal activity – but are a surrogate measure.

Front 6

Review

Back 6

•Asa whole the nervous system takes inputs (senses), performs computations andgenerates output (behaviours).

•Sodoes each part of the nervous system

•Differentparts of the nervous system perform different computations – so have differentfunctional roles – but they are very interconnected.

--> Howdoes the nervous system perform these computations?

- stop looking at gross brain areas,and start looking at the cells that make up the brain.

Front 7

Brain cell types

Back 7

Neurons – key information-transmitting braincell. Transmit and process informationusing electrical signals.

-Dendrites: collect inputs from other neurons

-Soma: cell body, contains nucleus(genetic material – DNA)

-Axon: axon hillock, - where nerveimpulse/action potential triggered (integrates all inputs)

-myelin sheath: increases speed of transmissionand axon terminal – whereneurotransmitter is released to signal to the next cell

Front 8

Brain cell types:

-Neurons

- Glia

•Astrocytes

•Oligodendrocytes

•Microglia

Back 8

Astrocytes- wrap processes around synapses andneurons, also contact blood vessels. Lotsof supportive roles

Oligodendrocytes – wrap myelin sheath around axon toinsulate the axon and allow impulses to travel faster

Microglia – the brain’s residentimmune cell – surveys brain for infection or damage and gobbles up damagedtissue or infection.

Front 9

Electrical signalling inneurons

Back 9

Electricity – Ohm’s Law

Current = potential x conductance

Conductor– charge can flow through the material.

Conductance is measure of how wellcharge can flow. – More conductance – electricity flows more easily so thecurrent is higher (like a big hole in pipe - lots of water can flow throughso there’s a large flow rate or current).

Theamount of current that flows depends on how much potential there is (how muchstored energy – how big is the battery?) and how easy it is for the current toflow through the circuit . As said in prev slide, to use the water analogy this isthe water pressure.

Current = potential / resistance

Resistanceis how much a material resists current flow. So if the resistance of a materialis high there is a smaller flow of charged particles and a smaller flow. (Likeif you make the hole in the pipe smaller – there’s more resistance to flow outof the pipe so the amount of water that gushes out of the pipe will besmaller).

Front 10

Conduction in nerves different to inwires

Back 10

•Hermannvon Helmholtz (1849) – measured speed of nerve conduction by stimulating frogsciatic nerve and measuring time to constrict muscle.

•Nerveconduction ~ 30-40 m/s, 1 million times slower than electricity flows down awire.

Front 11

Currents flow down nerves as a wave ofcharge movement

Back 11

•Chargedparticles don’t flow far along a nerve when stimulated

•Insteadcharge flows across the cell’s membrane.

•Thiscurrent changes the voltage across the membrane

•Thisvoltage change propagates along the axon, like a wave – this is the actionpotential. We’ll learn about this in next lecture.

Thiswave of current down an axon is known as the action potential.

Front 12

what is electrical potential?

Back 12

the difference in electric potential between the interior and the exterior of a biological cell

Front 13

How do cells signal electrically?

Back 13

•Movementof ions

•Electricallycharged particle

•E.g.sodium chloride = Na+ and Cl-

•Differentsizes

•Someion flux (flow) happens at rest – this sets the neuron up to be ready tosend an electrical signal

•Someion flux happens during signalling

•First,let’s consider the situation at rest – the resting membrane potential…

Front 14

theresting membrane potential

Back 14

•Cellsare surrounded by a lipid membrane

•Watersoluble things can’t pass through.

Potentialmeans voltage difference – cells have a baseline voltagedifference across the membrane. Thishappens because…

Water is slightly polarised – ithas negative bits (the Oxygen) and positive bits (the hydrogens)which means that charged stuff can bind to it and therefore things like ionsare soluble in water – also the heads of these phospholipid molecules

Tails aren’t charged so they don’tbind to water and stick together forming this layer inside the membrane

So water soluble things can’t getthrough.

Front 15

Concentration gradients

Back 15

Outside:

•Na+

•Cl-

•Bitof Ca2+

Inside:

•Proteins(-ve)

•K+

Front 16

Holes in the membrane: Ion channels

Back 16

Potassium“leak” channels let potassium (K+) through

from resting -> leak some k+ from inside to outside cell -> Electrical gradient: Now the inside isnegative relative to the outside (-70 mV)

This negative charge stopsmore potassium leaving the cell

Front 17

Electrochemical gradient

Back 17

A gradient of electrochemical potential, usually for an ion that can move across a membrane.

The gradient consists of two parts, the chemical gradient, or difference in solute concentration across a membrane, and the electrical gradient, or difference in charge across a membrane

Front 18

Equilibrium potentials

Back 18

•Potentialacross membrane at which there is no net flow of an ion

•Equilibriumpotential (E) dictated by concentration difference and ion charge

Tounderstand how ions move across membranes its useful to think about equilibriumpotentials

Whichdirection an ion flows is dictated by concentration difference across themembrane and the ion charge (because that affects how the electrical gradientwill affect the ion)

–> when both are balanced there’s no net flow –> themembrane potential (voltage) at which this happens is called the equilibriumpotential.

Lots of K inside cell so will tend to leave,and membrane potential has to get pretty negative to stop the K+ from leavingthe cell – so negative equilibrium potential –> -80mV – bit more negative thanthe resting membrane potential I just told you. Hmm!

Lots of sodium outside cell, sotends to go into cell, and will do that very readily when the inside isnegative relative to outside – but if membrane becomes really positive, ionswill stop entering

Front 19

Membrane potential

Back 19

•Setby electrochemical gradient and permeability of membrane to different ions

•Ifmembrane only permeable to potassium,

Em = EK+ =-80 mV

•ButEm ≈ -70 mV

•Membraneslightly permeable to sodium too (ENa+ = + 62mV).

•Therestingmembrane potential ofneurons is near to the equilibrium potential for potassium.

•Thisis because at rest the membrane is more permeable to potassium than any otherion (more K+ channels are open).

Front 20

Role of ATP– energy.

Back 20

Generally leakage of K+ out of and Na+into cell. Gradually this would depleteconcentration gradients. The ions need to pumped back to where they came fromwith the Na+/K+ pump,

Ionfluxes during AP don’t as they travel down electrochemical gradients. It’senergetically favourable forthem to flow – they “want” to.

Putting them back moves them against thesegradients – we have to use energy to do this – ATP.

Front 21

What sets the equilibrium potential for a given ion (at a given temperature)?

Back 21

The value of the equilibrium potential for any ion depends upon the concentration gradient for that ion across the membrane.

If the concentrations on the two sides were equal, the force of the concentration gradient would be zero, and the equilibrium potential would also be zero.

Front 22

What plays a major contribution to the resting membrane potential of the cell?

Back 22

What generates the resting membrane potential is the K+ that leaks from the inside of the cell to the outside via leak K+ channels

--> generates a negative charge in the inside of the membrane vs the outside.

At rest the membrane is impermeable to Na+, as all of the Na+ channels are closed.