hormones and neural circuits
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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 - PowerPoint PPT PresentationTRANSCRIPT
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