PCOL M2 Flashcards
EXPLAIN ORGANIZATION OF THE NERVOUS SYSTEM
IE AND EV to CNS = afferent
CNS TO IE AND EV = efferent
- are electrically excitable cells that process and transmit information via an electrochemical process
NEURONS
- Receive and integrate the input from other neurons and conduct this information to the cell body
- May be hundreds in every neuron
DENDRITES
Carries the output signal of a neuron from the cell body, sometimes over long distances
AXONS
Only one in every neuron, but may branch distally to contact multiple targets
AXONS
Makes contact with other neurons at specialized junctions
- end part of neuron
AXON TERMINAL
spaces between 2 neurons
synapses
old english in uk and us singular and the plural form of [spaces between 2 neurons]
UK = synapse [singular]
synapses [plural]
US = ganglion [singular]
ganglia [plural]
2 broad categories of Neuronal System in the CNS
- HIERARCHICAL SYSTEMS
- NONSPECIFIC OR DIFFUSE NEURONAL SYSTEM
- Include all pathways directly involved in sensory perception and motor control
- HIERARCHICAL SYSTEMS
o Information is processed sequentially by successive integrations at each relay nucleus on its way to the cortex
- HIERARCHICAL SYSTEMS sensory system
A lesion at any link incapacitate the system
- HIERARCHICAL SYSTEMS
Two types of cells (hierarchical)
Relay or projection neurons
Local Circuit neurons
about Relay or Projection neurons
Relatively large
Axons emit collaterals that arborize extensively in the vicinity of the neurons
Excitatory
glutamate
Interconnecting pathways transmit signals over long distances
About Local Circuit neurons
Small axons arborize in the immediate vicinity of the cell body
inhibitory
GABA or glycine
Recurrent feedback pathways Feed-forward pathways
- 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
- NONSPECIFIC OR DIFFUSE NEURONAL SYSTEMS
* Contain one of the monoamines (dopa, SE, NE)
* Neurotransmitters: Monoamines
* Receptors: Adrenergic receptors (metabotropic)
found in compact cell group called locus ceruleus located in the caudal pontine central gray matter
- NE cell bodies
explain The synaptic transmission
1 synthesis
2 storage vesicle
3. Release
4. Postsynaptic receptors
in the 5 step depends
5. uptake then metabolism
or
5. diffusion
Explain synaptic transmission of acetylcholine
asa pic
Explain synaptic transmission of norepinephrine
nasa pic
- 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
EXCITATORY POST SYNAPTIC POTENTIAL (EPSP)
- Provides a small local hyperpolarization
- Propagated by inhibitory neurotransmitters
- Generally results from opening of K+ and Cl- channels
INHIBITORY POST SYNAPTIC POTENTIAL (IPSP)
- Neurotransmitters are chemicals that take a nerve signal across the synaptic gap between a sending neuron, and a receiving one
NEUROTRANSMITTERS OF THE BRAIN
- Small molecule neurotransmitters
- Mainly amino acids and amines
- The “classical“
- Relatively larger
- The combination of two or more amino acids joined by peptide bonds
- The neuropeptide neurotransmitters
AMINO ACID NEUROTRANSMITTERS Two categories:
*the acidic amino acid [glutamate]
*the neutral amino acids [glycine and GABA]
- 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
- 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
- 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
- present on essentially all neurons in the CNS
- highly permeable to Ca2+ as well as to Na+ and K+ .
GLUTAMATE Ionotropic receptors
NMDA
- two requirements for NMDA receptor channel opening:
o Glutamate must bind the receptor and
o the membrane must be depolarized
- G protein-coupled receptors that act indirectly on ion channels via G proteins
- mGluR1–mGluR8 divided into 3 groups
GLUTAMATE Metabotropic receptors
- typically located postsynaptically
- activate phospholipase C, leading to inositol trisphosphate mediated intracellular Ca2+ release
Group I receptors
- 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
- inhibitory neurotransmitters typically released from local interneurons
GABA and GLYCINE
- spinal cord and brainstem
- selectively permeable to Cl− .
- Strychnine selectively blocks glycine receptors
o Glycine
- throughout the CNS
o GABA
- Ionotropic receptor that are selectively permeable to Cl-
- Mediate fast component of IPSP
GABA A
- Metabotropic receptors, selectively activated by Baclofen
- Inhibit Ca+2 channel or activate K+ channel
- Also inhibit adenylyl cyclase and decrease cAMP generation
GABA B
- ——- 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
- 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
- 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
involves disinhibition
o Indirect mechanism
involves blockade of potassium conductance
o Direct mechanism
- 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
- 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
- Result from overstimulation of dopamine receptors
Psychoses
- Caused by too little dopaminergic input from the substantia nigra into the striatum
Parkinson’s disease
- 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)
- 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
- 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
- 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
