Hormones and neural circuits

Lecture 4

Aims

to review main hormones actions through G-coupled receptors role of NO

to describe the basic neural circuits for repetitive action

to describe types of modulation by hormones simple behaviour: molluscan swimming

and feeding complex behaviour: insect ecdysis

Hormones

Amino acid and peptide Adenaline, acetylcholine, oxytocin, vasopressin, CCAP

Steroids ecdysone

Eicosanoids leukotrienes, prostaglandins

NO

NO Nitric oxide - a gas! synthesised from L-arginine by NOS

neurons (nNOS, epithelium eNOS) depends on Ca concentration

COO-

C

(CH2)3

NH

C

H2N

H

NH2+

Arginine

NOS

NADPH

+ O2

NAD+

COO-

C

(CH2)3

NH

C

H+H3N

N+

H2NH

OH

N-w-Hydroxyarginine

COO-

C

(CH2)3

NH

H+H3N + NO

NOS

C

O NH2

Citrulline

NO signalling

NO diffuses freely though cell membranes but not very far!

half life from 3-5s

soluble guanylyl cyclase activated by NO elevates cGMP

relaxes smooth muscle in blood vessels via PKG and an effect on IK(Ca)

important for heart-disease nitrate (nitroglycerin) used to reduce angina

Background to Viagra

cGMP normally broken down by phosphodiesterase

Viagra

Sildenafil - best selling drug selective for phosphodiesterase - type 5 [of

11]

termtadalafil [Cialis], vardenafil [Levitra]

Summary

NO – local transmission as gas; no vesicles

Modulation of single cells Single cells can be rhythmic

R15 in Aplysia sino-atrial node of vertebrate heart Purkinje fibres of heart

vertebrate heart

single cell rhythm

Rhythm at sinoatrial node

Modulation of heart rate

If – hyperpolarization activated Na+ current ACh accelerates rhythm Adrenaline slows

rhythm

activation curve:100% of If channels open here

ivabradine

new heart drug blocks If (note difference

from ACh)

Summary

NO – local transmission as gas; no vesicles

heart: single cell rhythm modulated in different ways to give same

effect

Neural circuits

central pattern generation role of reflexes (see 632)

Clione

Clione - a free swimming sea mollusc

swimming rhythm

alternation of up and down stroke of wings

Clione - ii

reciprocal inhibition up (8) / down (7)

post inhibitory rebound

78

78

78

Faster with 5-HT

CPB1 is serotonergic

heart

down interneuron

Molluscan feeding

Serotonin as modulator local neural release (CGC, hormonal signal in blood

What does it target? How does it act?

Target 1 : muscles

5-HT

myomodulincAMP

Target 2 : motoneurons

MCC is cerebral serotonergic cell in Aplysia; B21 is a buccal motoneuron

Target 3: sensory neurons

sense organ in one bathganglion in anotherStretch evokes twitches

add 5-HT to sense organ

use low Ca to show this effect is not due to action on ganglion

Target 4: interneurons

B4 is a motoneuronB35 an interneuron in CPG

control + 5-HT

fasterbigger EPSPquicker decline of EPSP

Summary

NO – local transmission as gas; no vesicles heart: single cell rhythm

modulated in different ways to give same effect

Serotonin: Action on all points of network Coordinated effect

some cells inhibited Similar data exist for dopamine,

octopamine, myomodulin, FMRFamide…

Insect ecdysis

Fundamental to growth and development 20-hydroxy-

ecdysone juvenile hormone

Manduca sexta ligature, extirpation,

transplantation, injection,

Fly life cycle

larva (3 instars)

adult

pupaegg

Moulting

weakening of old cuticle formation of new cuticle emergence

separation of old /new by air bubble (pre-ecdysis)

peristaltic waves to move forward out of old cuticle (ecdysis)

expansion : compression, intake of air (post-ecdysis)

Main peptide hormones

ETH EH FMRFamide CCAP Bursicon

ETH

26 aa peptide in Manduca

2 peptides in flies secreted by Inka

cells in response to

drop in ecdysone

ETH targets

Eclosion hormone (EH)

In Manduca, EH released from 2 cells in brain in response to ETH positive feedback to Inka cells (which

release more ETH …) In Drosophila, EH thought to play lesser

role; ecdysis delayed by 4 min similar role may be played by corazonin

FMRFamide

secreted from Tv neurons

first cells to be activated by ETH

strengthen muscle contractions

Tv-KO is not lethal

CCAP

CCAP from 5 pairs of SOG cells and 2 pairs/segment in abdomen

In Manduca, CCAP turns off pre-ecdysis and starts ecdysis (abdominal waves)

In Drosophila, CCAP-KO do not start contractions or evert head

Bursicon

140 aa important in tanning released from a

subset of CCAP-cells

Bursicon CCAP

Sequential response to ETH

Summary

NO – local transmission as gas; no vesicles heart: single cell rhythm

modulated in different ways to give same effect

Serotonin: Coordinated action on all points of network Similar data exist for dopamine,

octopamine, myomodulin, FMRFamide… Ecdysis: Sequential program of hormone

action