Molecular Neuroscience

by Revest, Patricia; Longstaff, Alan

• ISBN13: 9780387915197
• ISBN10: 0387915192
• Format: Paperback
• Copyright: 1998-08-01
• Publisher: Taylor & Francis

Summary

Clearly illustrated and concise guide for undergraduates; Use of didactic style to aid understanding; Well-selected examples from modern neuroscience to highlight key principles; Ideal introduction for all newcomers to the field; Molecular Neurosc

Table of Contents

Abbreviations	ix	(6)
Preface	xv
1 Introduction	1	(4)
2 Receptor cloning	5	(26)
Introduction	5	(1)
The amino acid sequence of a protein can be deduced by sequencing its DNA	5	(1)
Restriction enzymes can be used to cut DNA	6	(1)
Separation of DNA fragments by size	6	(2)
DNA molecules can be joined using ligases	8	(2)
rDNA is introduced into bacterial cells for cloning	10	(1)
Vectors are constructed using genetic engineering techniques	10	(3)
Several methods have been devised to sequence nucleic acids	13	(2)
A strategy for cloning a desired sequence	15	(6)
The nicotinic cholinergic receptor was sequenced by probing a cDNA library	21	(7)
Box 2.1. Labeling of oligonucleotide probes	28	(3)
3 Molecular anatomy of the nervous system	31	(14)
Introduction	31	(1)
Many neurotransmitters can be located by histochemistry	31	(2)
ELISA tests can detect a wide range of molecules	33	(1)
Some neurotransmitters can be located by specific uptake mechanisms	33	(1)
Receptors can be counted using receptor ligand-binding assays	34	(1)
In situ hybridization can determine patterns of gene expression	35	(1)
Different kinds of blotting can identify DNA, RNA and proteins	36	(1)
Differential hybridization and subtracted cDNA libraries can measure differences in gene expression	37	(1)
The polymerase chain reaction can produce large amounts of a specific DNA	38	(3)
Single-cell PCR	41	(1)
mRNA differential display uses PCR to study changes in gene expression	41	(2)
A large number of genes expressed in human brain have been identified	43	(2)
4 Voltage-gated ion channels	45	(32)
All excitable cells contain voltage-sensitive ion channels	45	(32)
Sodium channels were the first to be identified	45	(2)
Structure and function can be related at the molecular level	47	(4)
Voltage-gated calcium channels are responsible for diverse functions	54	(1)
Calcium channels have been cloned	55	(3)
How similar are sodium and calcium channels?	58	(2)
There is a large diversity of voltage-gated potassium channels	60	(3)
Genes for potassium channels have been identified in naturally occurring mutant flies	63	(6)
Not all K(+) channels belong to the same superfamily	69	(2)
Box 4.1. Voltage clamping	71	(1)
Box 4.2. Patch clamping	72	(2)
Box 4.3. Site-directed mutagenesis	74	(1)
Box 4.4. Chromosome walking	75	(2)
5 Ionotropic receptors	77	(26)
Introduction	77	(1)
Nicotinic acetylcholine receptors have been studied extensively	77	(3)
The M2 segments contribute to the ion pore	80	(5)
GABA is the major CNS inhibitory transmitter	85	(1)
GABA(A) receptors bind many different ligands	85	(3)
GABA(A) receptors heterogeneity is evident from pharmacology	88	(4)
GABA(C) receptors	92	(1)
Multiple glutamate receptors exist	93	(2)
Separate AMPA and kainate receptors can be distinguished	95	(2)
NMDA receptors	97	(4)
Properties of NMDARs were studied by coexpression	101	(2)
6 Metabotropic receptors and signal transduction mechanisms	103	(24)
Introduction	103	(1)
G protein-linked receptors activate a cascade of protein interactions	103	(1)
G protein-linked receptors form a superfamily of receptors	104	(2)
G protein-linked receptors share a common structure	106	(5)
There are many distinct G proteins	111	(2)
The actions of G proteins can be studied using a variety of techniques	113	(1)
G protein Alpha-subunits are linked to a range of effectors	114	(3)
G protein Beta Gamma-subunits can alter the activity of Alpha-subunits	117	(1)
Many ion channels are modulated by G proteins	118	(2)
Many growth factor receptors activate an intrinsic tyrosine kinase	120	(1)
Cyclic GMP levels are controlled by two separate pathways	121	(1)
Mutations in 7TM receptors underlie a variety of diseases	122	(1)
Dopamine receptors have been implicated in schizophrenia	123	(3)
Box 6.1. Antisense knockouts	126	(1)
7 Neurotransmitter release	127	(24)
Introduction	127	(1)
Neurotransmitter release at the neuromuscular junction is quantal	128	(1)
Neurotransmitter release at central synapses may consist of a single quantum	129	(1)
Neurotransmitter release is calcium dependent	129	(2)
Which calcium channels are responsible for neurotransmitter release?	131	(2)
A large number of proteins have been identified in nerve terminals	133	(1)
Neurotransmitter release involves a number of calcium-dependent steps	134	(1)
Vesicle recruitment may involve synapsin	134	(2)
SNAPs and SNAREs are involved in docking and then priming vesicles for release	136	(2)
Synaptophysin and physophilin may form the fusion pore	138	(1)
Synaptotagmin may be the calcium sensor involved in the final exocytotic event	139	(1)
Rab3A is involved in recycling of neurotransmitter vesicles	140	(1)
Neurexins are a target for neurotoxins	141	(1)
Recycling of synaptic vesicles may involve dynamin	142	(1)
Refilling of vesicles with neurotransmitter occurs via an antiport mechanism	143	(1)
Termination of neurotransmitter action is due to diffusion and binding	144	(2)
Lambert-Eaton myasthenic syndrome is a failure of neurotransmitter release	146	(1)
Box 7.1. Imaging calcium in cells	147	(1)
Box 7.2. Production of transgenic animals	148	(3)
8 Mechanisms of plasticity	151	(40)
The hippocampus is required for episodic memory	151	(2)
Long-term potentiation is an activity-dependent increase in synaptic strength	153	(3)
Both pre-and postsynaptic events appear to be involved in the maintenance of NMDAR-dependent LTP	156	(1)
Protein kinases are activated during LTP	157	(3)
Invertebrates currently provide the most complete evidence for nuclear signaling via cAMP in plasticity	160	(5)
A metabotropic receptor switch is required for LTP	165	(1)
Presynaptic mechanisms for induction of LTP	166	(7)
Long-term depression is a synaptic weakening	173	(5)
Voltage-dependent channels are implicated in plasticity	178	(1)
LTP may be a molecular model for some types of learning	179	(3)
Epilepsy is a chronic hyperexcitable state	182	(6)
Box 8.1. Electrophoretic mobility shift assay (EMSA)	188	(1)
Box 8.2. Floxed receptor knockouts	189	(2)
9 Molecular mechanisms in neurodegenerative disease	191	(24)
Introduction	191	(1)
Huntington's disease causes a specific pattern of neuronal loss	191	(3)
Excitotoxicity involves inappropriate activation of glutamate receptors	194	(4)
Parkinson's disease also causes degeneration of specific neurons	198	(4)
Alzheimer's disease causes severe dementia	202	(2)
AD may be caused by a number of different genes	204	(2)
The amyloid hypothesis depends on the abnormal deposition of BetaA	206	(2)
Aggregation of tau proteins underlies the formation of tangles	208	(1)
ApoE interacts with both BetaA and tau in an isoform-specific manner	209	(1)
Other hypotheses have been suggested for the cause of AD	210	(1)
New therapies may be based on understanding the molecular basis of AD	210	(1)
Common paths to oxidative stress and free radical damage in neurodegenerative disease	211	(1)
Box 9.1. Linkage analysis of DNA using RFLPs	212	(3)
Appendices	215	(2)
Appendix 1. Genetic code	215	(1)
Appendix 2. Single-letter code and three-letter abbreviations for amino acids	215	(1)
Appendix 3. Some second messenger-activated enzymes	216	(1)
Glossary	217	(10)
Further reading	227	(4)
Index	231