Brain cells

1791: Luigi Galvani demonstrated that nerves conduct electricity. Galvani connected a nerve from a frog's leg to a metallic wire. This was pointed to the sky during a thunderstorm and it produced muscular contraction of the frog's legs

1921: Otto Loewi demonstrated that neurons communicate with each other by means of chemical transmission. He took the still beating hearts of 2 frogs, one with a vagus nerve and one without. He placed them in 2 separate jars containing saline solution. The vagus nerve slows the heart. Loewi called the chemical vagusstoff. We now know it as the neurotransmitter acetylcholine

We now know that electrochemical signals are sent via individual nerve cells or neurons. Right up until the early 1900s, the idea that the brain was comprised of separate cells was widely doubted. Reticulists believed that the brain was a continuous network of interconnected fibres.

The nervous system is comprised of 2 types of cells: neurons, which receive information and transmit it to other cells, and glia, which have a number of complex functions.

1891: Santiago Ramon y Cajal modified the cell staining technique and was able to identify individual brain cells

1897: Charles Sherrington introduced the terms neuron and synapse.

Dendrites: receive messages from presynaptic terminals and transfer them to the body of the neuron. Some contain dendritic spines (small outgrowths) that increase their surface area allowing a greater number of connection

Axons: long tubes that carry information from the cell body to the terminal buttons. It can be covered in myelin. They vary considerably in length (1mm up to 1m)

Presynaptic terminal (terminal button): contains special chemicals called neurotransmitters. These are released into the synaptic cleft.

• Surround and hold neurons in place
• Supply nutrients and oxygen to neurons
• They insulate one neuron from another
• They destroy pathogens
• Remove dead neurons
• Play a role in the control of breathing
• Assist neurons to form synaptic connections

Types of glia

• Astrocytes: hold neurons in place, probide nourishment, and form the blood-brain barrier
• Oligodendrocytes: provide myelin, an insulating cover around the axons
• Microglia: contribute to clean-up of dead tissue. They're an important link with the immune system

A nerve impulse must be steadily maintained along its whole length and not get weaker the further it travels. Axons regenerate an initial signal at each point along their length. Those that have further to travel are made more efficient by the myelin sheath

A nerve impulse is an electrical current that travels along dendrites or axons due to ions. They move through voltage-gated protein channels in the neuron's plasma membrane. There are 2 types of channels in the membrane. When they open, they allow either sodium or potassium ions to travel through them. These voltage-gated channels open and close in response to an electrical voltage - they're affected by changes in the electrical change around them. Electrostatic gradient: positively charged ions are strongly attracted to negative ones and vice versa. Diffusion gradient: high concentrations of ions are attracted to areas of low concentration.

When a neuron is at rest (not firing), a charge difference is maintained between the inside and outside of the cell. The difference in charge is so that the inside of the cell is at around -70mV compared to the outside. Although called resting potential, there's an active process involved in maintaining it

Resting potential is produced and maintained by active transport using sodium potassium pumps. These pumps require considerable energy: up to 20% of the cell's energy is spent fuelling the sodium potassium pumps.

The pumps send sodium ions out of the cell and bring in potassium ions at a ratio of 3:2. Thus, the inside of the cell remains less positively charged compared to the outside.

Due to these pumps, there are more potassium ions inside the cell, and more sodium ions outisde. In addition, the cell membrane leaks potassium more than sodium, so that the inside of the cell becomes even more negatively charged compared to the outside. The tension between different concentrations of ions and their electrical charge means they're primed to fire and release

Action potential: positive electrical charge that travels down the length of a neuron's axon briefly reversing the membrane's polarity.

Initiation: it's triggered by the accumulation of positive electrochemical signals received from 100s-1000s of the terminal bulbs of other neurons. These travel to the soma, which initiates an action potential starting from the axon

Threshold: the firing of a neuron is an all-or-none event. To fire, a neuron must reach a threshold. The membrane potential must reach between -55 to -40mV. If it does, it starts a chain reaction along the length of the axon.

A nerve impulse begins when a stimulus disturbs the plasma membrane on a dendrite, causing sodium channels to open. If the change is enough, the increase in positive charge will cause sodium channels to open. Sodium floods into the cell, depolarising the membrane so that the change is reversed. The outside of the cell becomes more negative than the inside. This has a domino-like effect. Neighbouring voltage-gated sodium channels are affected and open, moving the depolarisation along the membrane. The moving depolarisation is called the action potential. It's a positive electrical charge that travels down the length of a neuron's axon briefly reversing its polarity

On neurons with long axons, the nerve impulse can take a long time to reach the terminal buttons. The myelin sheath can speed up the nerve impulse because the action potential jumps from each node of ranvier to the next. This is called saltatory conduction. 

Changes occur behind the action potential to restore the resting potential. The voltage-gated sodium channels close and voltage-gated potassium channels open. This allows a rapid flow of potassium ions out of the cell, repolarising the membrane so the inside is again negative relative to the outside is positive. The sodium potassium pumps then restore the resting potential. Action potentials last a few milliseconds before the cell restores the negative resting potential. Before the neuron returns to the resting potential, there is a period of time in which it cannot fire. During the refractory period, the sodium potassium pump restores the balance between the ions.

When an action potential arrives at the presynaptic terminal it causes voltage-gated calcium ion channels to open. Calcium ions diffuse into the cell and cause synaptic vesicles to bind with the presynaptic membrane and release their payload of neurotransmitters into the synaptic cleft.

The neurotransmitters bind with postsynaptic receptors. The effect of some neurotransmitters, such as acetylcholine, is to depolarise the receptive membrane turning it from negative to positive = Excitatory postsynaptic potential (EPSP). Acetylcholine causes sodium channels to open. Sodium ions rush in and if the membrane reaches threshold, the next neuron will fire.

Some neurotransmitters cause the postsynaptic membrane to hyperpolarise so that the inside becomes even more negative compared to the outside = inhibitory postsynaptic potential (IPSP). Postsynaptic neurons becomes less likely to reach threshold. Neurotransmitter gamma aminobutyric acid (GABA) causes negatively charged chloride ions (Cl-) to enter postsynaptic neurons.

Both EPSPs and IPSPs can affect the same neuron. It's the combined action of excitatory and inhibitory effects that determines whether an action potential will be initiated or not

After a neurotransmitter has achieved its effect, it must be inactivated. For acetylcholine, an enzyme in the synaptic cleft, acetylcholinesterase, breaks down the acetylcholine into acetyl CoA and choline. The release of the neurotransmitters from the receptors causes the sodium channel to close. The acetyl CoA and choline are taken back up into the presynaptic terminal for resynthesis (reuptake). The synaptic vesicles are also recycled and later filled with neurotransmitter molecules and are ready for another round of synaptic transmission

Acetylcholinesterase inhibitors (AChEls): these are found naturally in some venoms and poisons, but there are also drugs that are designed to increase the levels and duration of acetylcholine. AChEls have been used to treat cognitive impairments found in Alzheimer's, Parkinson's and schizophrenia.

There are at least 60 neurotransmitters. Some important ones include: acetylcholine, dopamine, GABA, glutamate, and serotonin.

Acetylcholine: a widely distributed excitatory neurotransmitter that triggers muscle contraction and stimulates the excretion of certain hormones. In the CNS, it's involved in wakefulness, attentiveness, anger, aggression, sexuality, and thirst. Alzheimer's disease is associated with reduced acetylcholine in certain regions of the brain.

Dopamine: a neurotransmitter involved in controlling movement, posture, and a range of higher-order cognitive functions. It modulates mood and plays a central role in positive reinforcement and dependency. Loss of dopamine in certain parts of the brain causes the muscle rigidity typical of Parkinson's disease.

GABA: inhibitory neurotransmitter that is widely distributed in the neurons of the cortex. Contributes to motor control, vision, and many other cortical functions. It plays an important role in regulating anxiety. Some drugs that increase the level of GABA in the brain are used to treat epilepsy and to calm the trembling symptoms of Huntington's disease.

Glutamate: major excitatory neurotransmitter. Associated with learning memory and visual awareness. Thought to be associated with Alzheimer's disease, whose first symptoms include memory disruptions. It plays an important role in seizure activity

Serotonin: contributes to various functions, such as regulating body temperature, sleep, mood, appetite, and pain. Depression, suicide, impulsive behaviour, and aggressiveness, all appear to involve imbalances in serotonin.

It is important to study the brain at the micro level, as changes in brain chemistry can affect one's personality. Imbalances in serotonin have also been shown to make people more impulsive and agressive.