# The Human Nervous System
* The nervous system transmits electric and chemical signals to coordinate the behaviors and actions of complex organisms such as humans. 

## Functions of the Nervous System
* Information is collected from the inside as well as outside of the body in the form of **sensory input**.
* This information is transmitted to the brain and spinal cord's processing areas. The subsequent  processing of this information by **integration** occurs in the brain.
* Post the processing of the information in the brain, impulses are conducted from the brain and spinal cord to the organs, muscles, and glands as **motor output**.

## Organization of the Nervous System

* There are two main divisions of the nervous system: the **peripheral nervous system (PNS)** and **the central nervous system (CNS)**.


### The Central Nervous System (CNS)
* The **brain** and **spinal cord** are part of the **CNS**.

### The Peripheral Nervous System (PNS)
* The  **PNS** comprises the **sensory (afferent)** and the **motor (efferent)** pathways.
* The motor pathway can be further divided into **somatic (voluntary)** and **autonomic (involuntary)** divisions based on the nature of the response.
* Lastly, there are two types of autonomic responses: **parasympathetic ("rest and digest")** and **sympathetic ("fight or flight")**.
* **Sensory receptors**: structures at nerve endings that register physical and environmental stimuli, such as pain and temperature.
* **Ganglia/ganglion** (plural/singular): a group of neuron cell bodies found outside the CNS.
* **Plexuses/plexus** (plural/singular): a network of nerves located outside the  CNS.

#### The Somatic Nervous System
- Only **one** motor neuron (also known as somatic motor fibers or alpha motor neurons) is required to reach its target/effector organ.
- Origin: the anterior horn of the spinal cord
- Target: Skeletal muscle
- The motor neuron produces acetylcholine (ACh) at the synapse, which binds to nicotinic receptors on muscles to trigger contraction.

#### The Autonomic Nervous System
- Utilises **two** motor neurons to reach its target/effector organ.
- **Pre-ganglionic neuron**
- Origin: brainstem/spinal cord
- Target: synapses with a ganglion
- **Post-ganglionic neuron**
- Origin: ganglion
- Target: effector organ (e.g., skeletal muscle, organ, etc.)



##### The Sympathetic Nervous System

###### Effects on Target Cells

##### The Parasympathetic Nervous System

###### Effects on Target Cells

###### Neurotransmitters Utilised by the Sympathetic and Parasympathetic Nervous Systems

### Afferent and Efferent Transmission

* Information is carried into a structure by an **afferent axon** and out of it by an **efferent axon**.
* **Afferent or sensory neurons bring in sensory information** to the CNS, while **efferent or motor neurons send motor information** from the CNS to the PNS.


## Cells of the Nervous System
### Neuron
* Fundamental unit of the brain and nervous system.
* Specialised, excitable cells that receive and transmit signals
* Do not divide (amitotic) upon reaching a certain developmental stage, except for in some areas of the hippocampus as well the olfactory epithelium.
* Have a high metabolic rate and require a steady supply of oxygen.
* Can last a lifetime with adequate nutrition.


#### Parts of a Neuron and their Functions
##### Dendrites
* Short processes that emerge from the cell body. A neuron may have several dendrites.
* Receive information from neighboring neurons.
* Dendritic cell membranes contain a variety of channels and receptors, including:
- **Ligand-gated ion channels or Ionotropic Receptors:**
- Quick response
- Neurotransmitters bind to allosteric sites which allow molecules to either activate or inhibit receptors. When activated, the channel opens.
- **GPCRs (G-Protein Coupled Receptors) or Metabotropic Receptors:**
- Slower response
- Neurotransmitter binds to receptor leading to:
- G-protein activation
- Activation of Second Messengers by G protein.
- Second messengers activate Protein Kinases
- Different membrane channels open as a result of phosphorylation.
* These receptors let positive or negative ions into the cell:
- **Excitatory Postsynaptic Potentials (EPSPs)** induce **depolarization**.
- **Inhibitory Postsynaptic Potentials (IPSPs)** induce **hyperpolarization**.
- EPSPs and IPSPs are also called **graded potentials**, which are transmitted to the cell body by dendrites.
- **Dendritic spines:** Small protrusions present on dendrites that serve as the postsynaptic contact site for many synapses.


##### Cell Body/Soma
The cell body performs the following functions:
* Receiving graded potentials via receptors on its membrane (similar to dendrites)
* Synthesis of proteins required for cell function:
- DNA from the nucleus is transcribed into messenger RNA (mRNA).
- mRNA is transported to the rough endoplasmic reticulum (also known as **Nissl bodies** in neurons) where it is translated into proteins.
- Proteins are then transported to the Golgi apparatus and packaged into vesicles.
* Neurotransmitters, enzymes, and membrane proteins are examples of proteins synthesized in the cell body.


##### Axon
* Projection from a specialised region of the cell body known as the axon hillock.The **axon hillock is the site of action potential generation.**
* The conducting region of a neuron; forms synapses with dendrites. 
* Each neuron has a single axon, which may reach a length of 1 meter or 3 feet.
* A nerve fiber is one long axon.
* **Axon collaterals:** axon branches.
* Transmits action potential from cell body to target cell (e.g., other neurons).
* Site of migration of cellular material between cell body and axon terminal.
* May be **insulated** with **myelin sheath**.
* **Axolemma**: plasma membrane of an axon. Responsible for preserving neuron membrane potential via ion channels.
* **Axon terminals**: ends of axons; release neurotransmitters $\rightarrow$ pass on signal to next neuron; reuptake neurotransmitters $\rightarrow$ regulate signals and recycle molecules.
* Clusters of axons are known as **nerves in the PNS** and **tracts in the CNS**.

##### Myelin sheath
- Only axons are myelinated
- Protects fibers; increases speed of action potential propagation.
- Produced by **oligodendrocytes in the CNS**, **Schwann cells in the PNS**.
- **Nodes of Ranvier**: gaps in myelin where action potential jumps from one node to the next (**saltatory conduction**).
- **Gray matter**: CNS regions containing nerve cell bodies and unmyelinated axons.
- **White matter**: CNS regions containing myelinated axons.


#### The Synapse
- Junction point of communication between two neurons.
##### History and Discovery
###### Sherrington's Experiment
- Investigated the neuronal circuit underlying the reflex arc for the withdrawal reflex in dogs.
- The reflex is not blocked when the spinal cord is severed from the brain. The reflex mainly requires the spinal cord. 
- Withdrawal reflex: Upon pinching the dog's foot, the dog flexes that leg after a short delay. 
- The impulse travels from the skin receptor $\rightarrow$ spinal cord $\rightarrow$ leg muscle during that delay.
- Sherrington calculated the speed of impulse conduction along the reflex arc and concluded that **synapses** between neurons were slowing down the speed of impulse conduction.
- **Presynaptic neuron:** Neuron delivering the signal.
- **Postsynaptic neuron:** Neuron receiving the signal.
- **Temporal and spatial summation:**
- Several weak pinches in quick succession = temporal summation.
- Several weak pinches from separate nearby regions = spatial summation.
- **Excitation and inhibition:** The same stimulus (pinch) activates certain muscles while inhibiting others. This suggested that synapses have the ability to significantly alter the information being transmitted.


###### Loewi's Experiment
- Investigated chemical transmission at synapses.
- Utilized 2 frog hearts that were placed in a simple salt solution (Ringer's solution).
- The hearts will continue to beat and the nerve supply to the heart can subsequently be isolated.
- The vagus nerve of the first frog’s heart was then repeatedly stimulated, decreasing its heart rate.
- The fluid around the first frog’s heart was collected and transferred to the second frog’s heart. The second heart also slowed down as a result.
- Loewi concluded that the chemical composition of whatever was released into the salt solution upon stimulation of the vagus nerve was responsible for neuronal communication.
- Chemical synapses convert electrical signals to chemical and are the most common type of synapse.
- Electrical synapses were discovered much later.

##### Neurotransmitter Release and Removal at the Synapse
- Action potential spreads along presynaptic axon $\rightarrow$ depolarizes presynaptic axon terminal $\rightarrow$ voltage-gated calcium channels open $\rightarrow$ release of neurotransmitter in synaptic vesicles via exocytosis is triggered $\rightarrow$ neurotransmitter binds to postsynaptic membrane receptor $\rightarrow$ excitation/inhibition in postsynaptic neuron (depending on neurotransmitter) $\rightarrow$ synaptic vesicles are retrived via endocytosis.
- Neurotransmitter is removed from the synaptic cleft by diffusion, degradation or reuptake.


#### Structural Classification of Neurons
- **Multipolar neurons**
- Have more than 3 processes with one being the axon and the rest being dendrites.
- Primarily serve as interneurons (a neuron whose dendrites and axon are completely enclosed within a single structure) within the CNS and as motor neurons which conduct impulses along efferent pathways.
- **Bipolar neurons**
- Have two processes (axon, dendrite) on opposite sides of the cell body.
- Sensory neurons found in distinctive sense organs (e.g., retina)
- **Pseudounipolar neurons**
- One neuronal process that splits into two branches.
- Function mainly in the PNS as first-order sensory neurons, sending impulses down afferent pathways.


### Neuroglia
Neuroglia or glial cells provide support to neurons in both the CNS and PNS.

#### CNS Neuroglia
##### Astrocytes
* The most abundant glial cells that serve a variety of functions.
* Contain foot processes that extend from the cell body.
* Provide structural and metabolic support for neurons by:
- Determining capillary permeability which is critical for the formation of the **blood-brain barrier** via tight junctions.  
- Controlling the chemical environment by **removing excess neurotransmitter** and **buffering potassium ions** accumulated in the extracellular fluid through potassium leak channels at rest and voltage-gated potassium channels during the repolarization phase of the action potential. 

##### Microglia
* Immune cells of the CNS.
* Phagocytize (the process by which a cell uses its plasma membrane to engulf a large particle) microbes and debris.

##### Oligodendrocytes 
* Forms myelin sheath.

##### Ependymal cells
* Line cavities of the brain and spinal cord
* Form a partially permeable barrier between cerebrospinal fluid (CSF) and tissue.
* Cilia assist in CSF circulation.

#### PNS Neuroglia
##### Satellite cells
* Function similarly to astrocytes but in the PNS.
##### Schwann cells (neurolemmocytes)
* Form myelin sheath.
* Involved in the regeneration of damaged peripheral nerve fibers.


### Summary of Terms Used to Describe Parts of the Nervous System


## Types of Cell Signaling

- Chemical signaling is the primary means by which cells communicate with one another.

For the purposes of this course, we will focus on paracrine and endocrine signaling.
- Many different types of chemicals can be utilized for signaling:
- **Paracrine** regulators (tissue hormones) have only localized effects on surrounding cells.
- Are dispersed by simple diffusion through interstitial fluids.
- Are quickly inactivated by enzymes after activating a receptor protein on a target cell.
- E.g. histamine.
- **Neurotransmitters**
- Released by neurons in response to electrical stimulation on a very short cell-to-cell range across synapses.
- **Neurohormones**
- Released into the bloodstream by neurons.
- **Hormones**
- Act over a longe-range.
- Released into the bloodstream by endocrine glands.

### Major Neurotransmitters and their Features


### Hormones
#### Major Endocrine Glands in the Human Body


#### List of Hormones and their Functions

#### Pituitary hormones

#### Hormonal Regulation by Negative Feedback

## Neuroanatomy

### Directional Terms
- Directional terms are used to determine one structure in relation to another.
- Some terminologies, such as dorsal or ventral, are relative to the axis of the CNS, therefore the direction these phrases define varies depending on whether they are used for brain areas or other body regions.
- Other terms, such as superior or inferior, retain their meaning across the whole body.
- **Anterior:** In front of; toward the face
- **Posterior:** Behind; toward the back
- **Superior:** Above; toward the head
- **Inferior:** Below; toward the feet
- **Medial:** Toward the middle
- **Lateral:** Toward the edge
- **Dorsal:** Toward the top of the brain or the back of the spinal cord
- **Ventral:** Toward the bottom of the brain or the front of the spinal cord
- **Rostral:** Toward the front of the brain or the top of the spinal cord
- **Caudal:** Toward the back of the brain or the bottom of the spinal cord
- **Ipsilateral:** Structures on the same side of the body.
- **Contralateral:** Structures on opposite sides of the body.


#### Anatomical Planes
- The nervous system can be examined using axes or planes.
- **Frontal or coronal plane:** A vertical plane that runs from the medial to lateral direction, dividing objects into front and back sections.
- **Sagittal plane:** A vertical plane running from the rostral to caudal direction, dividing objects into right and left sections.
- **Horizontal plane:** Divides objects into top and bottom sections.


#### Labeled Views of the Human Brain


#### Summary of Neuroanatomical Terms

### The Cranial Cavity
- The cranial cavity is the space within the skull that houses the brain.


#### The Ventricular System
- The nervous system begins developing as a tube surrounding a fluid canal.
- The canal persists into adulthood as the spinal cord's central canal and the ventricles, four fluid-filled compartments within the brain.


##### The Ventricles
- The ventricles are structures that produce and circulate **cerebrospinal fluid** around the cranial cavity.
- They are lined by ependymal cells, which create a structure known as the **choroid plexus**.
- **CSF is produced in the choroid plexus**.
- CSF is an ultrafiltrate of blood plasma with most of the proteins removed.
- It performs three primary functions:
- Protection: reduces neuronal damage from cranial injuries by acting as a cushion for the brain.
- Buoyancy: the brain's net weight is lowered by about 25 grams when immersed in CSF. This reduces the amount of pressure on the base of the brain.
- Chemical stability: the CSF generates an environment that allows the brain to function properly, for example, by maintaining a low extracellular $\mathrm{K+}$ concentration for synaptic transmission.


- There are **four** ventricles in total: the right and left lateral ventricles, the third ventricle, and the fourth ventricle.
- The left and right lateral ventricles are situated within their respective hemispheres in the cerebrum. Their "horns" extend into the temporal, occipital, and frontal lobes.
- The lateral ventricles connect with the third ventricle toward their posterior. The third ventricle is located at the midline and separates the left thalamus from the right thalamus.
- The third and fourth ventricles join in the center of the medulla.

###### Pathway of CSF flow through the Ventricular System

#### The Meninges
- Comprises three layers; are protective membranous covering of the brain and spinal cord.
- From superficial to deep: dura mater, arachnoid mater, pia mater 


#### The Blood-Brain Barrier

##### Components of the blood-brain barrier (innermost to outermost) 
- Endothelial lining of blood vessels with tight junctions located between endothelial cells, which help reduce permeability across the barrier.
- Basal lamina made of connective tissue.
- Astrocyte foot processes.
- Pericytes are also present.


##### Functions of the blood-brain barrier
Controls what leaves the bloodstream and enters the CNS neural tissue:
- **Substances that can passively diffuse:**
- Carbon dioxide, oxygen, and lipid-soluble compounds.
- **Substances that require transporters:**
- Water and electrolytes ($\mathrm{Na^+}$,$\mathrm{Cl^-}$).
- **Substances that should not pass:**
- Proteins, as they can function as neurotransmitters and produce undesired neural activity.

<!-- #### Graphical Representation of the Interactions Between the Blood-Brain Barrier, Meninges and Ventricular System
 -->

### The Spinal Cord
- Long, tubular bundle of nerve tissue surrounded by the bony vertebral column, meninges, and CSF.
- Central canal is continuous with the fourth ventricle and carries CSF through the spinal cord. 
- Extends from the brainstem to the lumbar region. 
- Information travels up the spinal cord through afferent (sensory) fibers and down via efferent (motor) fibers.
- White matter: both afferent and efferent fibers.
- Gray matter: cell bodies.
- Cell bodies are arranged in three columns known as "horns".

### Divisions of the Vertebrate Brain (Fish)


## Further Resources

* [Afferent vs Efferent Neurons: What Are They, Structure, and More](https://www.osmosis.org/answers/afferent-vs-efferent-neurons)
* [Anatomy and Physiology of the Nervous System Notes](https://www.osmosis.org/notes/Anatomy_and_Physiology_of_the_Nervous_System)
* [Anatomy & Physiology: 12.2 Nervous Tissue](https://open.oregonstate.education/aandp/chapter/12-2-nervous-tissue/)
* [Bioninja: Nervous System](https://ib.bioninja.com.au/standard-level/topic-6-human-physiology/65-neurons-and-synapses/nervous-system.html)
* [What is a neuron?](https://qbi.uq.edu.au/brain/brain-anatomy/what-neuron)
* [Neurology | Neuron Anatomy & Function](https://www.youtube.com/watch?v=qOmmqu6_g3s)
* [How Pathogens Penetrate the Blood-Brain Barrier](https://asm.org/Articles/2020/April/How-Pathogens-Penetrate-the-Blood-Brain-Barrier)
* [Foundations of Neuroscience - ANATOMICAL TERMINOLOGY](https://openbooks.lib.msu.edu/neuroscience/chapter/anatomical-terminology/ )
* [The Ventricles of the Brain](https://teachmeanatomy.info/neuroanatomy/vessels/ventricles/)
* [AustinCC - Neurotransmitters lecture notes](https://www.austincc.edu/sziser/Bio1724/1724LecNotes/LNExamIII/Neurotransmitters.pdf)