1. The Central Nervous System
The CNS consists of the brain & the spinal cord, immersed in the cerebrospinal fluid (CSF)
The brain consists of three main structures: the cerebrum, the cerebellum & the brainstem
Cerebrum composed of 2 cerebral hemispheres each made up of the cerebral cortex (grey matter), the basal nuclei & diencephalon (white matter)
Each hemisphere (left and right), consists of four lobes (frontal, parietal, occipital & temporal)

2. cerebral cortex
The outer layer of grey matter, approximately 2 mm thick, covering the entire surface of the cerebral hemispheres
It is made up of neurons & supporting glial cells
It functions to correlate information
from many sources to control
cognitive function (all aspects of
perceiving, thinking & remembering)

3. Basal Nnuclei (Ganglia)
The basal nuclei is a group of cell bodies deep in the white matter of the cerebral hemispheres beneath the cerebral cortex
Major components include the caudate, putamen, globus pallidus & substantia nigra
The basal nuclei functions to sensorio-motor integration & motor control

4. Cerebellum
The walnut-shaped structure situated at the base of the brain
The cerebellum is responsible for motor co-ordination, posture & maintaining equilibrium
It ordinates sensory input from the inner ear and the muscles to provide accurate control of position & movement

5. Brain Stem The stalk-like part of the brain connecting
the cerebral cortex, white matter & the spinal cord
Made up of the pons, the medulla oblongata & the midbrain
The brainstem acts as an important relay station
The brainstem contributes to the control of breathing, sleep & circulation
Every nerve impulse passing between the brain & the spinal cord must pass through the brainstem to allow the body to function normally

6. Other Parts of the Brain
Thalamus and Hypothalamus
The thalamus has wide connections with the cortex the basal ganglia, hypothalmus & brainstem
It is capable of perceiving pain
The hypothalamus has several functions, including control of the body’s appetite, sleep patterns, sexual drive & response to anxiety
Ventricles
Ventricles are a number of cavities within the brain
Ventricles are filled with CSF, which is produced within the ventricle wall
The CSF also surrounds the outer surfaces of the brain and ‘cushions’ the brain against trauma, maintains and control the extracellular environment, and circulates endocrine hormones

7. The limbic system
It a group of nerve pathways including structures deep within the temporal lobes, as the hippocampus & the amygdale
It is connected with the cerebral cortex, white matter & brainstem
the limbic system is involved in the control and expression of mood and emotion, in the processing and storage of recent memory, and in the control of appetite and emotional responses to food
The limbic system has been implicated in the
pathogenesis of depression & schizophrenia
The limbic system is linked with parts of
the neuro-endocrine & autonomic
nervous systems
hippocampus

8. Reticular Activating System
It is a collection of nuclei at the core of the brainstem
They receive input from the body’s sensory systems (sight, smell, taste, …etc), the cerebellum and cerebral hemispheres
Some neurons from the reticular formation project to meet motor neurons of the spinal cord and influence functions like CVS & respiratory control
In addition, there are also neurons projecting into most of the rest of the brain
The ascending fibers of the reticular formation form a network called the reticular activating system, which influence wakefulness, overall degree of arousal and consciousness (depression!)

9. Neurotransmission & Processing of Information
Two signaling mechanisms; action potentials & synaptic signals are the basis for all the information-processing in the brain
An action potential is initiated at a synapse and travels along the axon to the axonal terminal
The electrical signal is converted to a chemical signal; a neurotransmitter
It diffuses out of the neuron, across the synapse, to its neighboring neuron
At the postsynaptic neuron the chemical signal is converted back into an electrical signal once again

10. The Action Potential Resting neurons have a negative
membrane potential, caused by
a steady outflow of potassium ions & an impermeability to sodium ions
The action potential represents transient changes in this resting membrane potential
For most axons de-polarisation initiates the action potential
It causes a transient change in the membrane allowing the passage of sodium ion

11. The Synaptic Signal
50 nm
Once the action potential  reaches the axonal terminal,
the changed membrane potential triggers the activation of calcium channels
This allows elevation of the concentration of calcium ions in the pre-synaptic neuron 
Thereafter, synaptic vesicles fuse with the presynaptic membrane and one or more neurotransmitters are released into the synaptic cleft 
Neurotransmitters bind to specific receptors on the membrane of the postsynaptic neuron, or to an autoreceptor

12. Small Molecule Neurotransmitters

13. Neuropeptide Neurotransmitters
Corticotropin releasing hormone
Corticotropin (ACTH)
Beta-endorphin
SubstanceP
Neurotensin
Somatostatin
Bradykinin
Vasopressin
Angiotensin II

14. Serotonin
CNS contains only less than 2% of the total serotonin in the body
Serotonin is localized mainly in nerve pathways emerging from the raphe nuclei, a group of nuclei at the centre of the reticular formation
These serotonergic pathways spread extensively throughout the brainstem, the cerebral cortex and the spinal cord
In addition to mood control, serotonin has other functions, including the regulation of sleep, pain perception, body temperature, blood pressure & hormonal activity

15. Serotonin Receptors Seven classes, 5-HT1- 5-HT7
All 5-HT1A,1B,1D,1E,1F are inhibitory Gi-coupled
5-HT1A is a somatodentritic auto-receptor
5-HT1B,1D are postsynaptic & pre-synaptic auto-Rs
5-HT2 & 5-HT4 are excitatory receptors linked to Gq/11-PLC and Gs-AC respectively
5-HT3 is the only inotropic 5-HT receptor

16. Noradrenaline
Noradrenergic neurons are found in the locus coeruleus, the pons & the reticular formation
These neurons project to the cortex, hippocampus, thalamus & midbrain
The release of NA tends to increase the level of excitatory activity within the brain
Noradrenergic pathways are thought to be involved in the control of functions such as attention & arousal
locus coeruleus: A small area in the brainstem consisting of a pair of identical nuclei in the pons from which all brain connections, using NA, arise

17. Dopamine & Acetylcholine
It is of high density in the basal ganglia
Dopaminergic neurons are widely distributed throughout the brain in three important dopamine pathways:
The nigrostriatal,
The mesocorticolimbic,
The tubero-hypophyseal
DA deficit in Parkinson’s disease, DA over activity in schizophrenia
Acetylcholine
Cholinergic pathways are concentrated mainly in the brainstem
They are believed to be involved in cognitive functions, especially memory
Severe damage to these pathways is the probable cause of Alzheimer’s disease

18. Dopamine Receptors DA receptors are 7-TM G-protein coupled
D1-like (D1, D5) receptors are linked to Gi-AC
D1-like receptors mediate excitatory DA activity
D5 is abundant in limbic system, D1 in striaum, little in limbic system
D2-like (D2, D3, D4) are linked to Gs-AC
D2-like receptors mediate inhibitory activity of DA
D3, D4 receptors are located mainly in limbic s, & not in motor structures, unlike D2 receptors
Atypical neuroleptics (clozapine) have affinity of D3, D4> D2 → less extra-pyramidal side effects

19. Exciatatory Amino Acid Neurotransmission Glutamate & Aspartate
Exciatatory amino acid neurotransmitters, especially glutamate, are abundant in the CNS
Glutaminergic neurons in cerebral cortex provide the main excitatory cortical output to hippocampus, basal ganglia, thalamus & amygdala
Hippocampal glutaminergic neurons project to limbic structures possibly controling learning
Retinal glutaminergic neurons are the major excitatory pathways linked to photoreceptors
NMDA receptor antagonists including glycine-binding site blockers are investigated as potential antiepileptic agents or drugs that prevent ischemic brain damage after stroke/trauma

20. Exciatatory Amino Acid Receptors NMDA (N-Me-D-aspartate) & Non-NMDA Receptors
Inotropic tetrameric receptor permeable to monovalent cations, high permeability to Ca2+
Binding to glutamate→ ↑Ca2+ → Activation of Ca2+-dependent enzymes (PKC, NOS)→ response
It has 6 binding sites, 2 excitatory:
Glutamate binding sites
Glycine binding sites
and 4 inhibitory sites
Phencyclidine (PCP), voltage-gated Mg2+, Zinc, and polyamine binding site
Non-NMDA Receptors
4 subtypes named after their selective agonist:
Kainate R; Na+, K+-inotropic receptor, abundant in hippocampus
Quisqualate/AMPA iontropic Na+, K+- regulating receptor
L-AP4 metabotropic mGluR4,6,7,8 presynaptic receptors
They cause inhibition of pre-synaptic neurons
ACPD metabotropic receptors linked to PLC mediating excitatory effects

21. NMDA RECEPTOR

22. Inhibitory Amion Acid Transmission Gama-aminobutyric Acid (GABA)
GABA, the main inhibitory transmitter CNS in GABA pathways & GABA inter-neurones
50% of the inhibitory synapses in the brain are GABA mediated
Synthesized by glutamate decarboxylation
Pre- & post-synaptic GABA transporters terminate effect
GABAergic inter-neurons in retina, cortex, hippocampus, spinal cord, & cerebellum

23. Inhibitory Anion Acid Transmission Glycine
Formed from serine by hydroxyMe-transferase
Glycine receptors are inotropic Cl--channels, blocked by strychnine
Glycine is removed by uptake using two transporters GLYCT-1 & -2
Limited distribution
in spinal cord as inhibitory control over motor neurons
In brainstem, reticular formation & retina

24. Neuropeptides
Most important ones include: opioid peptides, angiotensin II, oxytocin, cholecystokinin, and vasopressin
All aforementioned peptides are excitatory except for opioid peptides that are inhibitory
Opiods will be discussed in detail later in separate session

25. Dopamine and Serotonin Pathway

26. Noradrenaline and GABA Pathway