Neural Prosthetic Engineering

Neurons and Neuronal Potentials

1

Neural Prosthetic Engineering NB

Neurons

• Neurons are the basic building blocks of our nervous system

• There are billions of neurons in our nervous system.• They are electrically excitable, enabling electric

stimulation.

• Once excited, they produce action potentials.

2

Neural Prosthetic Engineering NB

Number of Neurons

BiologicalNeuron?Thebasicfunctionalunitofthenervoussystem.

3

One estimate (published in 1988) puts the human brain at about 100 billion

(1011) neurons and 100 trillion (1014) synapses. A lower estimate (published in

2009) is 86 billion neurons, of which 16.3 billion are in the cerebral cortex,

and 69 billion in the cerebellum (Wikipedia, neurons)

1. Williams RW, Herrup K (1988). "The control of neuron number".

Annual Review of Neuroscience. 11 (1): 423–53. doi:10.1146/annurev.ne.11.030188.002231. PMID 3284447.

2.Azevedo FA, Carvalho LR, Grinberg LT, et al. (April 2009). "Equal

numbers of neuronal and nonneuronal cells make the human brain

an isometrically scaled-up primate brain". The Journal of

Comparative Neurology. 513 (5): 532–41. doi:10.1002/cne.21974. PMID 19226510.

utan

Neural Prosthetic Engineering NB

Structure of neurons

Image from Addiction Science Research and Education Center, the University of Texas

Basic neuron design Connection between neurons

4

Neural Prosthetic Engineering NB

Structure of neurons and Potentials they produce

• The basic neuron structure: cell body, dentrites and axons

• Synapses are the communication points between cells.• Axon from output neuron would make synapse(s) on

dendrite of input neurons.

• Pre-synapse, Post-synapse, and the post-synaptic potentials (PSP’s)

• EPSP vs. IPSP (excitatory PSP and Inhibitory PSP)• Action potentials travel on the axons and are like fast

digital pulses (All or none)- to be explained in detail.

• PSP are like analog waveforms, slow potentials.

5

Neural Prosthetic Engineering NB

Synaptic potentials

• Synapse : junction across one nerve cell excites another.1. Chemically coupled∼0.5msec delay2. Electrically coupled

• EPSP(Excitatory Post synaptic Potential) causes depolarization (excitation) of the next cell.

• IPSP(Inhibiting~) causes hyperpolarization.

Chemical transmitter

Presynaptic terminal of previous neuron

Synaptic cleft∼150Å

Postsynaptic terminal of next neuronl

6

Neural Prosthetic Engineering

Potentials of the neurons

spike

local field potential

how to discriminate between noise and LFP?

Neural Prosthetic Engineering NB

Membrane Potential of Neuron

• The neuron membrane is mostly lipid layer (insulating) except for the ion channels.

• In equilibrium, there exists an unbalance of ion concentrations across the membrane.

• These ionic imbalance across a permeable membrane causes a potential across it and this is called the

Resting Potential

• The Nernst equation is used to compute the resting potential for one ion.

• At this potential, chemical driving force (by diffusion) equals electrical driving force (by drift) on the ion.

8

Neural Prosthetic Engineering NB

Equilibrium Potential:Balancing the ion diffusion by electric field

Two forces of ion driving at resting membrane (resting ion channels)– Chemical driving force

• Diffusion of ions by concentration gradient

– Electrical driving force• Drift of ions by electrical

potential difference

Electrical driving force

Chemical driving force

Extracellular side

Cytoplasmic side

9

K+K+

K+

K+

K+

K+Na+

Na+Na+ Na+

Cl-

Cl-Cl-

Cl-

A-

A-A-

A-

- - - - - - - - -

+ + + + + + + +

Siegelbaum, S. A., & Hudspeth, A. J. (2000). Principles of neural science (Vol. 4, pp. 1227-1246). E. R. Kandel, J. H. Schwartz, & T. M. Jessell (Eds.). New York: McGraw-hill.

Neural Prosthetic Engineering NB

Membrane Potential

• Nernst Eq.(1889)

§ E : voltage inside membrane with respect to outside (outside is the ground potential)

§ U : mobility of cations(+) in the membrane§ V : mobility of anions(-) in the membrane§ So for one cation system, the first term can be regarded

as +1.

§ For one anion system, the first term is -1.§ RT/F : 25mV@RT (58 mV if log is base 10)§ First applied to physiology in 1902

E = u - v

u + v F

RT

[C]i

[C]o ln

Neural Prosthetic Engineering NB

Resting membrane potential

The resting potential of a cell is determined by the relative proportion of different types of ion channels that are open, together with the value of their equilibrium potentials

K+

Na+

Electrical driving forceChemical driving force

11Siegelbaum, S. A., & Hudspeth, A. J. (2000). Principles of neural science (Vol. 4, pp. 1227-1246). E. R. Kandel, J. H. Schwartz, & T. M. Jessell (Eds.). New York: McGraw-hill.

Neural Prosthetic Engineering NB

For Membrane that is permeable to Three Ions

• If the plasma membrane were permeable only to any single ion of K+, Na+, and Cl-, the potential difference across the membrane could be calculated by the Nernst equation.

12

Neural Prosthetic Engineering NB

Goldman-Hodgkin-Katz Eq.

Cytoplasm(mM) Extracellular

Fluid(mM)

Permeability ratio

at resting state

Permeability ratio

at active state

K+ 400 20 1 1

Na+ 50 440 0.04 20

Cl- 52 560 0.45 0.45

§ P : permeability

§ Hodgkin & Katz have found

Pk : PNa : PCl = 1: 0.04 : 0.45 at resting

X500

= 1: 20 : 0.45 at active

Neural Prosthetic Engineering NB

Action Potential of Neuron

• An excited (Stimulated) neuron (Above threshold) will experience change of ion permeability in short time

duration.

• At resting state, the membrane is permeable mostly to the K+ and Cl- ions.

• But at excitation, the the permeability to Na+ ions increases abruptly. This causes the depolarization of

the membrane (becoming more positive inside).

• Closing of Na+ gates and opening of K+ follow (hyperpolarization)

• Active pump will restore the initial state

14

Neural Prosthetic Engineering NB

Action potentials (APs)

15

http://anatomytutorials.weebly.com/action-potentials.html

Neural Prosthetic Engineering NB

Hodgkin-Huxley Model of Neuron

• Through elaborate experiments (voltage clamp experiments on Squid Axons), they were able to

explain the behavior of neurons using the voltage and

time dependence of permeability (conductance).

• They received Nobel prize of Physiology or Medicine in 1963 for this work.

16

Neural Prosthetic Engineering NB

Neuron membrane model

• Hodgkin Huxley model− In an active membrane, some conductances vary

with respect to time and the membrane potential.

17

Neural Prosthetic Engineering NB

METANEURON

• http://www.metaneuron.org/• ‘Free’ Interactive neural signal simulation software• To investigate the quantitative behavior of neuron in response to

different membrane properties and ion concentrations• Current pulse stimulation with an intracellular electrode• Based on the Hodgkin-Huxley equations• Six lessons: resting membrane potential, membrane time

constant, membrane length constant, axon action potential, axon voltage clamp and synaptic potential

• Newman M. and Newman E., “Metal Neuron: A free neuron simulation program for teaching cellular neurophysiology”, The journal of undergraduate neuroscience education (June), Spring 2013, 12(1), A11-17

18

Neural Prosthetic Engineering NB

Intracellular Recording:Action potentials (APs)

19

http://anatomytutorials.weebly.com/action-potentials.html

Electrolyte Solution

Glass Pipette

Metal Wire Electrode

cell

Neural Prosthetic Engineering NB

Extracellular Neural Recording:Compound Action potentials (CAPs) and Local Field Potentials (LFPs)

20

• If your metal electrode is outside several neurons, the electrode will record action potentials from multiple number of neurons. This is the CAPs. In this case, the amplitude of the potentials are attenuated significantly. (Extracellular Recording)•Together with the CAPs, the post synaptic potentials are recorded in a summated form. This is the LFP. This potential is a lot slower.

0.6 1.1

0.4

0.2

0

Am

plitu

de (

mV

)

Time (s)

CAP (spikes)

LFP

Neural Prosthetic Engineering NB

Cortical Signals Recorded from Brain

using Microelectrode

ParietalReachRegion(PRR)

21Hwang, Eun Jung, and Richard A. Andersen. "Effects of visual stimulation on LFPs, spikes, and LFP-spike relations in PRR." Journal of neurophysiology105.4 (2011): 1850-1860.

Neural Prosthetic Engineering NB

Reference-Hodgkin, Alan L., and Andrew F. Huxley. "A quantitative

description of membrane current and its application to

conduction and excitation in nerve."The Journal of

physiology 117.4 (1952): 500-544.

-Newman M. and Newman E., “Metal Neuron: A free

Neuron simulation program for teaching cellular

neurophysiology”, The journal of undergraduate

neuroscience education (June), Spring 2013, 12(1), A11-17

22