Paper : 06 Animal Physiology

Module : 06 Synapse and Neuromuscular Junction

Development Team

Principal Investigator : Prof. Neeta Sehgal

Department of Zoology, University of Delhi

Co-Principal Investigator : Prof. D.K. Singh

Department of Zoology, University of Delhi

Paper Coordinator : Prof. Rakesh Kumar Seth

Department of Zoology, University of Delhi

Content Writer : Dr. Sarita Nanda1, Dr. K P Mishra2, Dr. Anju Jain1
1Daulat Ram College, University of Delhi
2 Defence Institute of Physiology and Allied Sciences

Content Reviewer : Prof. Neeta Sehgal

Department of Zoology, University of Delhi

Animal Physiology
ZOOLOGY
Synapse and Neuromuscular Junction
 Description of Module

Subject Name ZOOLOGY

Paper Name Zool 006 Animal Physiology

Module Name/Title Neurotransmission

Module Id M06: Synapse and Neuromuscular Junction

Keywords Synapse, Neuromuscular Junction, Gap junction, Synaptic cleft,

Synaptic transmission, Neurotransmitter, Acetyl Choline,
Depolarization.

Contents:

1. Synapse
1.1. Introduction
1.2. Types of synapse
1.3. Structure of synapse
1.4. Events of synaptic transmission
2. Neuromuscular junction
2.1. Introduction
2.2. Structure of neuromuscular junction
2.3. Acetyl choline receptor
3. Summary

Animal Physiology
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Synapse and Neuromuscular Junction
 1. Synapse

1.1. Introduction:

In the nervous system, a synapse is defined as a major structure that permits a nerve cell to
pass an electrical or chemical signal to the adjacent nerve cells. In a most common synaptic
junction, the plasma membrane of axon of the signal-passing presynaptic neuron comes into
close apposition with the membrane of dendrites of the target postsynaptic neuron. Although,
almost no physical continuity between pre and postsynaptic elements is observed. As the
nervous system is composed of billions of specialized electrical excitable neurons, efficient
communication through synapse is very much crucial to the normal functioning of brain. The
process by which synaptic information is communicated to the adjacent neuron is called
synaptic transmission. A single neuron is mainly made up of three parts: nerve cell body,
dendrites and axon (Figure 1). When dendrites receive a strong enough signal from a
neighbouring neuron or from more than one neighbouring neurons, the resting electrical
potential becomes depolarized due to flow of ions through voltage gated ion channels. This
electrical signal by forming wave of depolarization travels down the cell's axon reaches to
axon terminal and passes to the adjacent nerve cells via synaptic structure.

Fig. 1: synaptic structure

Animal Physiology
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Synapse and Neuromuscular Junction
 Not only neurons, glial cells mainly astrocytes also exchange information with the synaptic
neurons and thereby respond to synaptic activity. Glial cells are the central player of
glutamatergic neuronal physiology (Mendez et.al.2016).

1.2. Types of synapse:

Nervous system contains a huge number of synapses which may vary in shape, receptor
composition, neurotransmitter involvement and electrical nature. Synapses are divided into
different types either on the basis of site of contact or signal transmission.

Fig. 2: Classification of synapse

On the basis of site of contact, synapses are divided in to four types (Figure 2):

I. Axodendritic synapse: Axodendritic synapse refers to the synapse between the axon
terminal of presynaptic neuron and the dendrites of postsynaptic neuron. It is the most
common type of synapse present in the nervous system. Axodendritic synapse is a kind
of chemical synapse as the impulse is transmitted by chemical components named
neurotransmitter.
II. Axosomatic synapse: Axosomatic synapse refers to the junction between axon
terminal of presynaptic neuron and the cell body of postsynaptic neuron.
III. Dendrodendritic synapse: Dendrodendritic synapse refers to the junction between
two different neurons. It is also one type of chemical synapse that receives
depolarizing signal from incoming action potential and causes influx of calcium ions

Animal Physiology
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Synapse and Neuromuscular Junction
 that intern leads to release of Neurotransmitter molecules to propagate the signal the
post synaptic neuron. Signaling mechanism in this kind of synapse utilizes Na+ and
Ca2+ pumps. Recent researches indicate bi-directional signaling of dendrodendritic
synapses (Shepherd GM 1996). Neurons may form dendrodendritic synapses to
compensate neuronal injury and loss of axon (Hamori J 2009). Dendrodendritic
synapses play an important role in neuroplasticity (Figure 3).

Fig. 3: Axosomaic, axodendritic, axoaxonic and dendrodendritic synapse.

IV. Axoaxonic synapse: Axoaxonic synapse refers to the synaptic junction of axon
terminal of one neuron with either the initial axon segment or an axon terminal of
another nerve cell.

On the basis of signal transmission, synapses are divided in to two types:

i. Electrical synapse: Electrical synapse is defined as a gap junction-mediated connection

between neighbouring neurons. It is found in all nervous systems, including human nervous
system. Electrical synapse conduct nerve impulses at a much faster rate than that of chemical
synapse although recent research indicates that these two modalities of transmission of
impulse interact closely, during development and also in the adult brain (Alberto E. Pereda
2014). At a gap junction, the membranes of communicating neurons come extremely close to
form the synapse. The distance between pre and postsynaptic neuron is almost 3.5 nm.
(Kandel et.al., 2000). The pore diameter of a gap junction channel is comparatively much

Animal Physiology
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Synapse and Neuromuscular Junction
 larger than the pores of other ion channels. As a result most of substances from presynaptic
cytoplasm can simply diffuse to the cytoplasm of the postsynaptic neurons. Not only the ions,
this channel also permits substances with a molecular weights up to hundred Daltons. ATP
and other important intracellular metabolites, like second messengers are also transferred
between neurons via electrical synapse. The major function of electrical synapse is to
synchronize the electrical activity among populations of neurons in response to a stimulus
(Figure 4).

Fig. 4: Schematic representation of electrical and chemical synapse

ii. Chemical synapse: Chemical synapse is defined as a specialized biological junction

through which neurons signal to each other or to non-neuronal cell via secretion of chemical
messenger. It is the most common type of synapse in the nervous system. Human nervous
system is composed of a huge number of chemical synapses; In case of young children the
number is almost 10,000 trillion. At a conventional chemical synapse the pre synaptic neuron

Animal Physiology
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Synapse and Neuromuscular Junction
 and post synaptic neuron remains separated by a narrow gap known as synaptic cleft. It is
about 20 nm wide junctional region and remains filled with watery fluid. Synaptic
transmission through chemical synapse involves sequence of events that ultimately forms
either EPSP or IPSP in post synaptic neurons depending on the nature of neurotransmitter
(either excitatory or inhibitory). Chemical synapse is very much crucial to the biological
computations that underlie perception and thought.

1.3. Structure of synapse:

A conventional Synaptic structure includes presynaptic neuron, synaptic cleft and

postsynaptic neuron. The presynaptic neuron is involved mainly in the storage and release of
neurotransmitter whereas the postsynaptic neuron is involved in reception of the
neurotransmitter. Each branch of axon terminal contains a multiple number of vesicles such
as agranular vesicles, granular vesicles, coated vesicles, cisternae and endosomes. Agranular
vesicle is also also known as synaptic vesicle. It is spherical, 35-50nm in diameter and
contains neurotransmitter. Synaptic vesicles contain small molecule neurotransmitters like
glutamate, glycine, catecholamines, serotonin or ACh. The granular vesicles are 80nm-
160nm in diameter and usually contain neuropeptides. Actin filaments are very much
important for movement of synaptic vesicles toward presynaptic membrane for fusion. An
important phosphoprotein synapsin I, modulates neurotransmitter release in the synaptic cleft.
(Landis & Reese 1983, Hirokawa et al. 1989, Greengard et al. 1994, Hilfiker et al. 1999). Not
only synapsin and F-actin, presence of two other structural components, microtubules and
fodrin (a brain isoform of spectrin), are also important in presynaptic terminal. The region in
the presynaptic terminal, formed by the membrane and a dense collection of proteins which
mediates neurotransmitter release is known as Active zone. The initial events of synaptic
transmission take place at the active zones. The postsynaptic part contains very high
concentration of receptor proteins or ligand gated ion channels for receiving the
neurotransmitter. Binding of neurotransmitter to the receptor causes flow of ions into the post
synaptic neuron which ultimately leads to formation of EPSP and IPSP. In case of excitatory
synapse neurotransmitters like glutamate, acetylcholine binds with their respective receptors
and causes flow of positive ions towards the post synaptic cell where binding of inhibitory

Animal Physiology
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Synapse and Neuromuscular Junction
 neurotransmitter like GABA with their receptor causes opening of ion channel that permits
ions like Cl- and forms IPSP.

1.4. Events of synaptic transmission:

2. Neuromuscular junction

2.1. Introduction:

A neuromuscular junction is defined as a special type of chemical synapse formed by the

motor neurons and a muscle fibre. Motor neurons originating from the spinal cord innervate
mainly the skeletal muscle fibres. Impulse transmission through motor neuron causes
muscular contraction via neuromuscular junction .Not only that the junction is also very
much important for maintenance of normal muscle tone. The process of impulse transmission
via neuromuscular junction is very similar to that of synaptic transmission in CNS.

Animal Physiology
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Synapse and Neuromuscular Junction
 Fig. 5: A neuromuscular junction

2.2. Structure of neuromuscular junction:

Neuromuscular junction is composed of motor neurons, synaptic cleft and skeletal muscle
cell. The cell bodies of motor neurons are present in the ventral horn of the spinal cord where
the axon terminal gives rise to fine processes that run along the skeletal muscle cells.
Neurotransmitter filled vesicles remain concentrated in active zone of the axon terminal.
Active zone is anatomically and biochemically specialized for release of neurotransmitter
molecules as the plasma membrane of active zone shows clustering of voltage sensitive
calcium channels. Depolarization of axon terminal increases the local concentration of Ca2+
which stimulates exocytotic release of neurotransmitter in the synaptic cleft. Another
filamentous protein synapsin is also present in active zone and helps in clustering of synaptic
vesicles. The surface of synaptic vesicle is composed of two groups of proteins-docking
proteins and elements of fusion pore. Docking proteins of vesicle interacts with docking
protein of pre-synaptic membrane of the synapse, create a docking complex. Complementary
proteins of both presynaptic and vesicle membrane form fusion pore, as a result stored
neurotransmitter begins to leak out through the pore. In case of vertebrates, motor neurons of
neuromuscular junction are cholinergic in nature and thereby release acetylcholine (ACh) in
the synaptic cleft, which diffuses through the synaptic cleft and binds to specialized ligand

Animal Physiology
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Synapse and Neuromuscular Junction
 gated cation channel in the cell membrane of the muscle fibre. Acetylcholine molecules after
binding, open ion channels, and as a result sodium ions diffuse into the muscle cell (Figure
5).

2.3. Acetyl choline receptor:

Acetyl choline receptor is a kind of integral membrane protein. Along with neuromuscular
junction acetyl choline receptors are also located in central nervous system and autonomic
nervous system.

Fig. 6: Types of acetyl choline receptor

There are two major types of acetylcholine receptor- Nicotinic acetylcholine receptors and
Muscarinic acetylcholine receptors (Figure 6). These two receptor subtypes are named after
plant components that stimulate them. The nicotine ACh receptor is excitatory in nature
(Giocomo 2005). Actually it is a Na+ and K+ ion channel that opens after binding of acetyl
choline in contrast Muscarinic acetylcholine receptors is a G protein coupled receptor and
usually inhibitory in nature (Figure 7). Although few in number nicotine ACh receptors are
also present in the central nervous system of insects (Yamamoto Izuru 1999). The receptors,
In vertebrates nicotinic ACh receptors are classified into N1 (present in neuromuscular
junction) and N2 (present in CNS, autonomic ganglia and adrenal medulla) type. In both case,
it is a 290 kDa protein (Unwin N 2005) containing five subunits, arranged symmetrically to
form a central pore. In embryo, the receptor is composed of two α1, one β1, one γ, and one δ
subunits but in adult brain it is composed of two α1, one β1, one δ, and one ε subunits. Each
subunit is again composed of four membrane spanning segments named as M1, M2, M3 and
M4.

Animal Physiology
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Synapse and Neuromuscular Junction
 Fig. 7: Nicotinic acetylcholine receptor

Binding of acetyl choline or other agonist to the active site of the channel causes
conformational change in the channel that ultimately leads to channel opening (Colquhoun
2004). Channel opening causes inward movement of positively charged sodium ions.
Actually nAChR is a special type of non-selective cation channel. Muscarinic acetylcholine
receptors are also very much important as these mediate diverse physiological functions
(Figure 8). Recent research indicates that, there are five subtypes of muscarinic receptor (M1-
M5). M1, M3 and M5 remains coupled to Gq/11 and activate phospholipase C which
ultimately leads to intracellular mobilization of Ca2+ ion and activation of protein kinase C.
On the other hand M2 and M4 are coupled to Gi/o, and causes inhibition of adenylyl cyclase
activity that in turn leads to hyperpolarisation of the cell membrane in different excitable
cells.

Animal Physiology
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Synapse and Neuromuscular Junction
 Fig. 8: Muscarinic acetylcholine receptor

An efficient enzyme, Acetyl cholinesterase is responsible for termination of a single event of

neurotransmission at cholinergic synapse of neuromuscular junction. The enzyme is
responsible for degradation the neurotransmitter acetylcholine.

It rapidly hydrolyses the neurotransmitter into choline and acetate, thereby it plays a very
essential role in cholinergic neurotransmission. Acetyl cholinesterase is also localized in non
neuronal glial cells within the CNS (Brightman et.al. 1959). Acetyl cholinesterase is the
major targets of action in case of most potent toxins including insecticides and snake venom
(Silman et. al. 2000). Inhibition of AChE is effective for the treatment of different
neuromuscular disorders like myasthenia gravis (MirJana 2013).

Conclusion: This chapter reviews the structural and functional organization of different types
of synapses and neuromuscular junction. The chapter should provide the reader with an
appreciation of all events of neuronal and neuromuscular transmission.

Animal Physiology
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Synapse and Neuromuscular Junction
 3. Summary:

 There is no physical continuity between pre and postsynaptic elements.

 Synapses are connections between neurons.

 Synapses are divided into different types either on the basis of site of contact or signal
transmission.

 Electrical synapse is gap junction-mediated connection.

 Chemical synapses involve neurotransmitter molecules for communication among the

neurons.

 Depending on the nature of neurotransmitter released in the synaptic cleft, either

EPSP or IPSP is formed in the postsynaptic membrane.

 A neuromuscular junction is a chemical synapse formed between motor neurons and a

muscle fibre.

 Depolarization of axon terminal increases Ca2+ concentration and leads to release of

neurotransmitters.

 Acetyl choline receptors are ligand gated ion channels.

 Opening of acetyl choline receptor causes flow of positive ions within the post
synaptic membrane of muscle cell.

 Acetyl cholinesterase is responsible for termination of a single event of

neurotransmission.

Animal Physiology
ZOOLOGY
Synapse and Neuromuscular Junction