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Neural control
Aim
 Outline basic structure and function of the nervous
system
 Outline the ways in which the nervous system
controls food intake
What’s in a nervous system?
 CNS has
neurons 109
 glia 3 • 109
 blood vessels

 developmentally
Fore-brain
 Mid-brain
 Hind-brain
 Spinal cord

What is a neuron?
 Parts of a
neuron
dendrite
 soma
 axon

How do we know what neurons look like?
 silver staining
 fluorescent dyes
 antisera
Resting potential
 Cells are all
negative
 contain K+
 outside Na+
 anions e.g. Cl have semipermeable
membranes
Animation of resting potential
 Bezanilla

http://nerve.bsd.uchicago.edu/
Summary so Far
 Brains made of neurons and glia
 All cells have resting potentials
 Normally maintained passively by balance of
diffusion and electrical forces
Extracellular action potential
time →
Intracellular recording
50 mV
zero
50 mV
0.5s
0.02s
Action potential
 membrane
becomes
permeable to
Na+
 Na+ floods in
diffusion
 electrical

 K+ still goes out
Role of Na+
 Two crucial properties of
the Na+ current
starts at a voltage
threshold
 stops itself

-30mV
open
1ms
 Arise from Na+ channel
channel is voltage
sensitive and opens
 closes with a second
mechanism

closed
inactivated
-70mV
Animation of Na channel
 http://nerve.bsd.uchicago.edu/testna8.html
TTX kills
Chemical connections
 release chemical transmitter
 respond with receptors
 advantages



effective
excite or inhibit
variable gain
 disadvantages

slower than electrical [??]
Synaptic connections
 Examples from snail neurons

Excitation

Inhibition
Transmitter release
Uptake and drugs
 Transmitters recycled by transporters
 Vesicles filled by transporters
 Major pharmaceutical target


Prozac – a SSRI – selective serotonin uptake inhibitor
Cocaine – blocks dopamine and serotonin (++) uptake
Pharmacology of receptors
 many kinds of transmitters and their
receptors
ACh, adrenaline
 glutamate, glycine
 serotonin, dopamine
 peptides: FMRFamide, CCK, NPY,

 most transmitters have multiple types of
receptors
 separate pharmacologically
Pharmacology of receptors
 Nicotinic ACh receptor
agonist - nicotine,
succinylcholine
 antagonist - curare,
bungarotoxin

 Muscarinic ACh
receptor
agonist - muscarine
 antagonist - atropine

Ionotropic & Metabotropic
 Ionotropic
receptor binding opens hole
 ions flow through

 metabotropic
receptor binding activates Gprotein
 requires second messenger
 7 transmembrane format
 phosphorylates another
protein [e.g. channel]

Peptides as neurotransmitters
 oxytocin



released from neurons in the hypothalamus
milk letdown
uterine contraction at birth
 substance P


Arg Pro Lys Pro Gln Gln Phe Phe Gly Leu Met
transmission of painful signals
cellular
damage
to skin
spinal cord
Summary - neurotransmission
 transmitter is stored in vesicles
 vesicles released by local Ca influx following action
potential
 transporters are major drug targets
 multiple kinds of transmitter

ACh, 5-HT, dopamine, peptides
 different receptors

ionotropic / metabotropic
How much do we need to eat for
homeostasis?
 digestion – metabolic rate – thermoregulation
 role of nervous system
Insulin & glucagon
Ghrelin “hunger hormone”





release from gut when blood sugar is low
elevated in Anorexia nervosa
peaks before meal
enhance fat deposition
prevent synthesis →
leaner mice
 causes release of
growth hormone
 ghrelin used to treat some cases of short stature
If homeostasis fails?
 Human who gains 1 kg over 10 years – extra 59MJ


44 GJ normal energy intake over this time
0.1% excess
 Hunger varies inversely with body weight
 Metabolism varies directly with body weight
 WHO estimate 1.6 billion adults overweight, 0.4
billion obese (BMI >30kg/m2)

up to 8% of health costs
What stops us eating?
 Short term

NTS
 stomach distension
 CCK (cholecystokinin)
 Long term

hypothalamus
 leptin
 insulin
CCK
long term:
adiposity
short term:
satiety
Leptin
 obese ob/ob mice – fail to synthesize leptin

perceived starvation in midst of plenty
 obese db/db mice have no leptin receptor
How does leptin act?
 receptors in



brainstem
 satiety
Nucleus accumbens
 reward
hypothalamus
 peptide neurotransmitters
Agouti-related peptide
Neuropeptide Y
pro-opiomelanocortin
cocaine and amphetamine
related transcript
α-melanocyte-stimulating
hormone
Badman & Flier Science 2005;307:1909-14
Ways to treat obesity?
 Manipulation of body weight




behavioural
 diet, exercise
surgical
 most effective, but high cost and high mortality risk
pharmacological
 1930s – increase energy expenditure (Thyroxine,
Dinitrophenol)
 1940s - “Rainbow Pills,” amphetamine, thyroxine,
digitalis, and a diuretic
 1992 – 1997 fenfluramine [+ phentermine] modulate 5HT signaling in hypothalamu
all associated with serious heart disease [RPs with
addiction]
Current pharmacological treatments
 Orlistat - a lipase inhibitor


with diet and exercise
2-3 kg more weight loss than placebo
 rimonabant – a cannabinoid-1 (CB-1) receptor
antagonist


6 - 7 kg more weight loss
safety concerns depression and related psychiatric
problems
 sibutramine – a reuptake blocker of 5-HT and
noradrenaline


amplifies satiety signals
2.5 – 5.5 kg weight loss
Summary
 Brains made of neurons and glia
 Resting potentials maintained passively by balance
of diffusion and electrical forces
 Properties of Na and K channels determine action
potential
 Multiplicity of transmitters each with several kinds
of receptors
 Range of peptides control food intake & energy
homeostasis
 No magic bullet to control obesity – many
redundant pathways, development of resistance
Reading …
 PowerPoints on VLE or at
http://biolpc22.york.ac.uk/003C/
 Schmidt-Nielsen, K (1997) Animal Physiology CUP
Books, etc
 Purves, D (et al) (2008)
Neuroscience Sinauer 4th ed
 Badman & Flier Science
2005;307:1909-14