1
Q
EXPLAIN ORGANIZATION OF THE NERVOUS SYSTEM
A
IE AND EV to CNS = afferent
CNS TO IE AND EV = efferent
2
Q
- are electrically excitable cells that process and transmit information via an electrochemical process
A
NEURONS
3
Q
- Receive and integrate the input from other neurons and conduct this information to the cell body
- May be hundreds in every neuron
A
DENDRITES
4
Q
Carries the output signal of a neuron from the cell body, sometimes over long distances
A
AXONS
5
Q
Only one in every neuron, but may branch distally to contact multiple targets
A
AXONS
6
Q
Makes contact with other neurons at specialized junctions
- end part of neuron
A
AXON TERMINAL
7
Q
spaces between 2 neurons
A
synapses
8
Q
old english in uk and us singular and the plural form of [spaces between 2 neurons]
A
UK = synapse [singular]
synapses [plural]
US = ganglion [singular]
ganglia [plural]
9
Q
2 broad categories of Neuronal System in the CNS
A
- HIERARCHICAL SYSTEMS
- NONSPECIFIC OR DIFFUSE NEURONAL SYSTEM
10
Q
- Include all pathways directly involved in sensory perception and motor control
A
- HIERARCHICAL SYSTEMS
11
Q
o Information is processed sequentially by successive integrations at each relay nucleus on its way to the cortex
A
- HIERARCHICAL SYSTEMS sensory system
12
Q
A lesion at any link incapacitate the system
A
- HIERARCHICAL SYSTEMS
13
Q
Two types of cells (hierarchical)
A
Relay or projection neurons
Local Circuit neurons
14
Q
about Relay or Projection neurons
A
Relatively large
Axons emit collaterals that arborize extensively in the vicinity of the neurons
Excitatory
glutamate
Interconnecting pathways transmit signals over long distances
15
Q
About Local Circuit neurons
A
Small axons arborize in the immediate vicinity of the cell body
inhibitory
GABA or glycine
Recurrent feedback pathways Feed-forward pathways
16
Q
- Contain one of the monoamines (—-,—-,—-)
- Pathways emanating from the reticular formation
- Some peptide-containing pathways
- Small, approximately 1500 on each side of the brain (rat)
- Axons are very fine and unmyelinated
- Neurotransmitters: —–
- Receptors: —-
- The system is implicated in functions such as sleeping and waking, attention, appetite, and emotional states
Types of Ion-channel and Neurotransmitter Receptors in the CNS
A
- NONSPECIFIC OR DIFFUSE NEURONAL SYSTEMS
* Contain one of the monoamines (dopa, SE, NE)
* Neurotransmitters: Monoamines
* Receptors: Adrenergic receptors (metabotropic)
17
Q
found in compact cell group called locus ceruleus located in the caudal pontine central gray matter
A
- NE cell bodies
18
Q
explain The synaptic transmission
A
1 synthesis
2 storage vesicle
3. Release
4. Postsynaptic receptors
in the 5 step depends
5. uptake then metabolism
or
5. diffusion
19
Q
Explain synaptic transmission of acetylcholine
A
asa pic
20
Q
Explain synaptic transmission of norepinephrine
A
nasa pic
21
Q
- Provides a small depolarization
- Due to the excitatory transmitter acting on an ionotropic receptor, causing an increase in cation permeability
- Generally results from opening of Na+ channels
A
EXCITATORY POST SYNAPTIC POTENTIAL (EPSP)
22
Q
- Provides a small local hyperpolarization
- Propagated by inhibitory neurotransmitters
- Generally results from opening of K+ and Cl- channels
A
INHIBITORY POST SYNAPTIC POTENTIAL (IPSP)
23
Q
- Neurotransmitters are chemicals that take a nerve signal across the synaptic gap between a sending neuron, and a receiving one
A
NEUROTRANSMITTERS OF THE BRAIN
24
Q
- Small molecule neurotransmitters
- Mainly amino acids and amines
A
- The “classical“
25
* Relatively larger
* The combination of two or more amino acids joined by peptide bonds
2. The neuropeptide neurotransmitters
26
AMINO ACID NEUROTRANSMITTERS Two categories:
*the acidic amino acid [glutamate]
*the neutral amino acids [glycine and GABA]
27
* Released into the synaptic cleft by Ca2+ -dependent exocytosis
* Mediates excitatory post synaptic transmission
* Activates both ionotropic and metabotropic receptors
GLUTAMATE - Vesicular glutamate transporter (VGLUT)
o Ionotropic receptors include;
* NMDA –R
* KA-R
* AMPA-R
o All are composed of four subunits
28
* GluA1–GluA4 subunits
* Majority contain the GluA2 subunit and permeable to Na+ and K+ , but not to Ca2+
* Some are present on inhibitory interneurons, lack the GluA2 subunit and are also permeable to Ca2+
GLUTAMATE Ionotropic receptors
AMPA
29
* high levels in the hippocampus, cerebellum, and spinal cord
* formed from a number of subunit combinations (GluK1–GluK5)
* permeable to Na+ and K+ and in some subunit combinations can also be permeable to Ca2+
GLUTAMATE Ionotropic receptors
KA (Kainate) Receptor
30
* present on essentially all neurons in the CNS
* highly permeable to Ca2+ as well as to Na+ and K+ .
GLUTAMATE Ionotropic receptors
NMDA
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* two requirements for NMDA receptor channel opening:
o Glutamate must bind the receptor and
o the membrane must be depolarized
32
* G protein-coupled receptors that act indirectly on ion channels via G proteins
* mGluR1–mGluR8 divided into 3 groups
GLUTAMATE Metabotropic receptors
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* typically located postsynaptically
* activate phospholipase C, leading to inositol trisphosphate mediated intracellular Ca2+ release
Group I receptors
34
* typically located on presynaptic nerve terminals and act as inhibitory autoreceptors
* Activation causes the inhibition of Ca2+ channels, resulting in inhibition of transmitter release
* Are activated only when the concentration of glutamate rises to high levels during repetitive stimulation of the synapse
* Activation also causes the inhibition of adenylyl cyclase and decreases cAMP generation
Group II and group III receptors
35
* inhibitory neurotransmitters typically released from local interneurons
GABA and GLYCINE
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- spinal cord and brainstem
* selectively permeable to Cl− .
* Strychnine selectively blocks glycine receptors
o Glycine
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- throughout the CNS
o GABA
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* Ionotropic receptor that are selectively permeable to Cl-
* Mediate fast component of IPSP
GABA A
39
* Metabotropic receptors, selectively activated by Baclofen
* Inhibit Ca+2 channel or activate K+ channel
* Also inhibit adenylyl cyclase and decrease cAMP generation
GABA B
40
* ------- responses are mediated by both muscarinic and nicotinic receptors
* Muscarinic effects are slower than nicotinic effects
* CNS responses are mostly mediated by G-protein coupled muscarinic receptors
* Degraded by cholinesterases
ACETYLCHOLINE
41
* Most noradrenergic neurons are located in the locus caeruleus or the lateral tegmental area of the reticular formation
* An amine, excitatory transmitter of the brain and smooth muscle
* All receptors are metabotropic
* Hyperpolarizes the neuron by increasing potassium conductance via the Alpha-2 receptor
* Enhances excitatory inputs in most areas of the CNS by both indirect and direct mechanisms
NOREPINEPHRINE
42
* Induce arousal, heighten mood
* Impaired monoamine (NE, SE and Dopa) neurotransmission has been associated with depression
* Drugs that induce monoamine release are indicated for attention deficit disorder and narcolepsy
NOREPINEPHRINE
43
involves disinhibition
o Indirect mechanism
44
involves blockade of potassium conductance
o Direct mechanism
45
* Synthesized from dopa
* Degraded by Monoamine oxidase A (MAO-A) in the brain and MAO-B outside the CNS and by catechol-O-methyl transferase (COMT)
* Receptors are:
o D1–like (D1 and D5 ); and
o D2 -like (D2 , D3 , D4 )
o all are metabotropic
* Major pathways are the projection linking the substantia nigra to the neostriatum and the projection linking the ventral tegmental region to limbic structures, particularly the limbic cortex
* Generally exerts a slow inhibitory action on CNS neurons [containing substantia nigra neurons, where D2-receptor activation opens potassium channels via the Gi coupling protein ]
DOPAMINE
46
* Important dopaminergic pathways
o Nigrostriatal pathway (from the substantia nigra to striatum)
o Neurons of the chemoreceptor trigger zone (CTZ) of the medulla – controls vomiting
o Projections from the hypothalamus to the intermediate lobe of the pituitary – thought to regulate prolactin release
47
* Result from overstimulation of dopamine receptors
Psychoses
48
* Caused by too little dopaminergic input from the substantia nigra into the striatum
Parkinson’s disease
49
* Formed from tryptophan (hydroxylated, then decarboxylated)
* Released from inhibitory neurons
* Stimulates 5HT receptors (more than a dozen)
o All receptors are metabotropic, except 5HT3 (ionotropic)
* Has inhibitory actions in most areas of the CNS
* Has been implicated in the regulation of virtually all brain functions, including;
o perception, mood, anxiety,
o pain, sleep, appetite,
o temperature,
o neuroendocrine control, and
o aggression
* Depression, Attention Deficit Disorder and Headaches have been attributed to serotonergic imbalances
5-hydroxytryptamine (5-HT, serotonin)
50
* Exclusively made by neurons in the tuberomammillary nucleus (TMN) in the posterior hypothalamus
* Modulate arousal, attention, feeding behavior, and memory
* Receptors are H1 to H4
o all are metabotropic
* Centrally acting antihistamines are generally used for their sedative properties
* Antagonism of H1 receptors is a common side effect of many drugs including some tricyclic antidepressants and antipsychotics
HISTAMINE
51
* Generally packaged in large, dense core vesicles
* Released neuropeptides may act locally or may diffuse long distances and bind to distant receptors
* Most ------- receptors are metabotropic and primarily serve modulatory roles in the nervous system ----------
* Implicated in a wide range of CNS functions including;
o reproduction,
o social behaviors,
o appetite,
o arousal,
o pain,
o reward, and
o learning and memory
o Opioid peptides
o Neurotensin
o Substance P
o Somatostatin
o Cholecystokinin
o Vasoactive Intestinal Polypeptide (VIP)
o Neuropeptide Y
o Thyrotropin-releasing hormone (TRH)
o The Opioids
* Endorphins, enkephalins and dynorphins are opiate receptor agonists
* All opioid receptors are metabotropic
Mu, kappa, delta
* In times of stress and pain, endogenous peptides act at opiate receptors (to relieve pain) Neuropeptides
Neuropeptides
52
* Released from primary sensory neurons in the spinal cord and brainstem and causes a slow excitatory postsynaptic potential
* Plays an important role in transmitting pain stimuli
Substance P
PHARMACOLOGY
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