Neurons, Communication and Transduction

Adapted from Steven Stahl MD, PHD

BASIC ANATHOMY AND PHYSIOLOGY

Anatomy and Physiology of The Neuron

• Neurogenesis, neuronal selection and migration occur before birth.

• Differentiation, myelination and synaptogenesis continue throughout entire life

• Competitive elimination is a process of brain restructuring that occurs in adolescence.

Synaptic Neurotransmission and Neurodevelopment

Neuronal organelles

• Peripheral proteins (proteins who live in the cytoplasm) are made on free polysomes and transported into the axon and dendrites.

• Integral or secretory proteins (proteins that are inserted into a membrane) are made on the rough endoplasmic reticulum, transported to the Golgi apparatus where they are packed into vesicles – ready for transport.

Protein synthesis

Peripheral protein synthesis

Synthesis of Membrane and Secretory Proteins

Some Protein Synthesis Occurs in The Dendrites

BASIC NEUROTRANSMISSION

Classic Neurotransmission

• The postsynaptic neuron can communicate with the presynaptic neuron (such is the case with endogenous canabinoids, NO and NGF).

Retrograde Neurotransmission

• Neurotransmission can occur without a synapse(by diffusion of the neurotransmitter to sites that are distant from its own synapse).

Volume Neurotransmission

• There are few dopamine reuptake pumps in the prefrontal cortex. The excess dopamine diffuses and finds receptors on other neurons.

Volume Neurotransmission of Dopamine in The Prefrontal Cortex

• Autoreceptors are situated on the same neuron and cause inhibition of transmission.

• For instance dopamine diffuses out of the synapse in the prefrontal cortex and stimulates the autoreceptors on the same neuron, thus inhibiting dopaminergic transmission.

Volume Neurotransmission to Autoreceptors on Monoamine Neurons

Inhibitory Volume Transmission

SIGNAL TRANSDUCTION

• Refers to communication between the genome of the presynaptic neuron and the genome of the postsynaptic neuron.

• It can happen both ways: the genome of the postsynaptic neuron can also communicate back with the genome of the presynaptic neuron.

• Signal transduction is a slow process taking hours or days.

Signal Transduction

Signal Transduction is a Two Way Street

• The cascade of events that take place after the stimulation of the postsynaptic receptors.

• The third messenger can be a KINASE which adds phosphate groups to proteins to create phosphoproteins.

• The third messenger can also be a PHOSPHATASE which removes phosphate groups from phosphoproteins

• The balance between kinases and phosphatases determines the downstrean chemical activity.

Signal Transduction Cascade

• G protein linked systems• Ion channel-linked systems• Hormone linked systems• Neurotrophin-linked systems

Neurotransmitters activate G protein linked systems and ion channel linked systems. Both of these systems activate genes in the cell nucleus.

Four Types of Signal Transduction Cascade

• The G protein linked system works through a cascade involving cAMP and Protein kinase A.

• The ion channel systems works through Calcium and calcium modulin kinase.

Both of these systems activate genes in the cell nucleus by phosphorylating a protein there called CREB (cAMP response element-binding protein).

• Certain hormones (like estrogen and steroids) enter the neuron, bind to their receptors in the cytoplasm, forming a hormone nuclear receptor complex. This complex enters the nucleus and interact with hormone response elements (HRE) to trigger activation of specific genes.

• The neurotrophin system activates a series of kinase to trigger gene expression, which may control synaptogenesis and neuron survival. Ras is a G protein, Raf is a kinase, MAPK is mitogen activated protein kinase and GSK3 is glycogen synthase kinase 3.

Signal Transduction Cascades

Four Most Important Signal Transduction Cascades