Important to destigmatizing mental disorders is understanding that they are diseases just like physical ones. They are a result of abnormalities in brain function. Thus, a knowledge of neuroscience is vital to internalizing this. Here is a brief refresher:

Part 1­– Introduction to the Brain

 

—Central Nervous System—

Forebrain

Cerebrum- higher order functioning, control of voluntary behavior, thinking, planning.

Left and right hemispheres connected by corpus callosum.

Cerebral cortex- sheet of tissue covering outermost layer of cerebrum. Aka gray matter. Wrinkled appearance of brain attributed to it. Has 4 parts.

-Frontal lobe: Motor movements, higher cognitive skills, personality, emotional makeup

-Parietal lobe: sensory processes, attention, language

-Occipital lobe: processes visual information, recognition of shapes and colors

-Temporal lobe: process auditory information, integrate information from other senses. Plays role in short-term memory through hippocampal formation and learned emotional responses through amygdale

Basal ganglia- cerebral nuclei deep in cerebral cortex, help coordinate muscle movements and reward useful behaviors

Thalamus- passes most info to cerebral cortex after helping to prioritize it

Hypothalamus- controls appetites, defensive and reproductive behaviors, and sleep-wakefulness

Midbrain

2 pairs of small hills called colliculi, play critical role in visual and auditory reflexes and relaying this type of info to the thalamus

Clusters of neurons which regulate activity in widespread parts of CNS and important for reward mechanisms and mood

Hindbrain

Pons and medulla oblongata control respiration, heart rhythms, and blood glucose levels.

Cerebellum- 2 hemispheres. Movement and cognitive processes that require timing, Pavlovian learning.

Spinal cord

Extension of brain. Receives sensory info from all parts below head.

Uses this info for reflex responses to pain and relays sensory info to brain and its cerebral cortex.

Spinal cord generates nerve impulses in nerves that control muscles and then viscera, through reflex activities and voluntary commands of the cerebrum.

17 in (43 cm) long. Vertebral Column protects it.

—Peripheral Nervous System—

Contains nerves and small concentrations of grey matter called ganglia.

Somatic nervous system- connects neurons of CNS with parts of body interacting with outside world. Cervical region- neck and arms. Thoracic region- chest. Lumbar and sacral region- legs.

Autonomic nervous system- neurons connecting CNS with internal organs. Divided into:

Sympathetic nervous system- mobilizes energy and resources during times of stress and arousal.

Parasympathetic nervous system- conserves energy and resources during relaxed states, such as sleep

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Neuron- nerve cells, basic working units of brain. Specialized cells designed to transmit info to other nerve cells, muscle, or gland cells.

Cell body- cytoplasm and nucleus.

Axon- extends from cell body. Gives rise to many smaller branches before ending at nerve terminals.

Dendrites- Extend from cell body and deliver messages to other neurons.

Synapse- contact point where neurons talk to each other.

Dendrites are covered with synapses formed by the ends of axons from other neurons.

Axon-Range from centimeter to meter length. Electrical impulses sent across axon to send or receive messages. Many covered with myelin sheath, made from specialized cells called glia, which accelerates transmission of signals across axon.

Glia- Glia that make up myelin sheath- oligodendrocytes, known as Schwann cells in PNS. 10 times more glia than neurons in brain. Glia transport nutrients to neurons, clean up brain debris, digest parts of dead neurons, hold neurons in place.

Ion channel- open and close while sending nerve impulses. Selectively permeable, water-filled molecular tunnels that pass through cell membrane and allow ions or small molecules to leave or enter the cell. Flow of ions creates electric current that produce voltage changes across neuron’s cell membrane.

Action potential- Neuron’s switch to internal positive from negative charge when a nerve impulse begins and a dramatic reversal of electrical potential occurs on cell membrane. The action potential passes through the axon’s membrane at speeds up to several hundred miles an hour, so a neuron can fire impulses multiple times a second. These voltage changes trigger release of neurotransmitter

Neurotransmitters- brain’s chemical messengers. Released at nerve terminals, diffused across synapse and bind to receptors on surface of target cell (usually neuron but can also be glia or muscle cell). These receptors act as on-and-off switches for next cell. Each receptor has distinctly shaped regions that each recognize dif chemicals. This interaction alters target cell’s membrane potential and trigger’s response from target cell such as generation of action potential, contraction of muscle, stimulation of enzyme activity, or inhibition of neurotransmitter release.

Acetylcholine- First neurotransmitter to be discovered, 80 years ago. ACh. Released by neurons connected to voluntary muscles, causing them to contract, and by neurons controlling heartbeat. Also a transmitter in many areas of the brain. Ach is synthesized in axon terminals. When action potential arrives at nerve terminal, calcium ions rush in and ACh is released into synapse and then attracts to receptors. In voluntary muscles this action opens sodium channels and causes them to contract. ACh is then broken down by the enzyme acetylcholinesterase resynthesized into nerve terminal. Antibodies that block a type of ACh receptor cause myasthenia gravis, a disease characterized by muscle weakness and fatigue. Less is known about ACh in the brain, but theories- critical for normal attention, memory, and sleep. ACh-releasing neurons die in Alzheimer’s so drugs that inhibit acetylcholinesterase and increase ACh in the brain are used.

Amino Acids- Widely distributed throughout body and brain. Bilding blocks of proteins. But certain amino acids can be neurotransmitters. Glycine and GABA (gamma-aminobutyric acid) inhibit firing of neurons. Activity of GABA is increased by benzodiazepines (such as valium) and anticonvulsant drugs. In Huntington’s disease, GABA-producing neurons in brain centers controlling movement degenerate and they cause uncontrollable movements. Glutamate and aspartate act as excitatory signals activating, among others, N-methyl-d-aspartate (NMDA) receptors which affect learning and memory, and development and specification of  nerve contacts. Stimulation of NDMA receptors can cause beneficial changes in brain but overstimulation can cause nerve cell damage and cell death. This is what oftentimes happens as a result of stroke or trauma. Drugs that block/stimulate NDMA activity has promise for disorders.

Catecholamines- includes dopamine and norepinephrine, which are each widely present in PNS and brain. Dopamine in 3 dif circuits: regulates movement (so ppl with Parkinon’s disease have trouble with moving bc of dopamine deficits in the brain there and thus are treated with levodopa, a substance from which dopamine is synthesized), regulates emotion and cognition (linked to schizophrenia (so some psychotic symptoms are treated by drugs which block certain dopamine receptors), and regulates endocrine system (dopamine directs hypothalamus to manufacture hormones and hold them in pituitary glad for release into bloodstream or trigger release of hormones held in cells in the pituitary). Deficiencies in norepinephrine occur in patients with Alzheimer’s, Parkinson’s, and Korsakoff’s syndrome, a cognitive disorder associated with alcoholism. Because these conditions lead to memory loss and decline in cognitive functioning, ppl think norepinephrine is involved in learning and memory. Norepinephrine is secreted by sympathetic nervous system throughout body to regulate heart rate and blood pressure. Acute stress increases release of norepinephrine from sympathetic nerves and the adrenal medulla, the innermost part of the adrenal gland.

Serotonin- particularly present in brain and other tissues, particularly blood platelets and lining of digestive tract. In brain serotonin is important factor in sleep quality, mood, depression, anxiety. Serotonin regulates diff switches associated with diff emotional states, and these switches can be manipulated by analogs, chemicals with molecular structures similar to that of serotonin. Fluoxetine- drug that alters serotonin’s action, used to relieve depression and OCD

Peptides- short chains of amino acids linked together synthesized in cell body and greatly outnumber classical transmitters above. In 1973 ppl discovered opiate receptors on neurons in several regions of brain, suggesting brain may make substances similar to opium. Soon scientists made the discovery of the opiate peptide in the brain. It resembles morphine, an opium derivative used to kill pain. This peptide was renamed enkaphalin, meaning “in the head”. Soon other types of opiod peptides were discovered. These were named endorphins, meaning “endogenous morphine”. Precise role of naturally occuring opiod peptides is unclear. Hypothesis is- they’re released by brain in times of stress to minimize pain and provide adaptive behavior. Some sensory nerves, tiny unmyelinated C fibers, contain a peptide called substance P which causes the sensation of burning pain. The active component of chili peppers is capsaicin which releases substance P.

Trophic factors- substances necessary for the development, functioning, and survival of specific groups of neurons. These small proteins are made in brain cells, released locally in brain, and bind to receptors expressed by specific neurons. There are also genes that code for receptors and are involved in signaling mechanisms of trophic factors. This finding should help discover more about how trophic factors work in the brain. And should be useful in design of new therapies for degenerative and developmental disorders, like Alzheimers and Parkinsons.

Hormones- Endocrine system also important communication system. Endocrine : hormones :: nervous : neurotransmitters. Pancreas, kidneys, heart, adrenal glands, gonads, thyroid, parathyroid, thymus, fat all sources of hormones. Endocrine system acts on neurons in brain that control pituitary gland. Pituitary gland secretes factors into blood which act on endocrine glands to increase or decrease hormone production. This pituitary-endocrine communication is called the feedback loop. Important for sex, stress, emotion, appetite, body functions like growth, metabolism, reproduction, energy use. Brain responding to hormones shows it’s very malleable and capable of responding to environmental signals. Brain has receptors for thyroid hormones and 6 classes of steroid hormones, which are synthesized from cholesterol- androgens, estrogens, progestins, glucocorticoids, mineralocorticoids, and vitamin D. The receptors are found in selected populations of neurons in brain and relevant organs in body. Thyroid and steroid hormones bind to receptor proteins that in turn bind to DNA and regulate actions of genes. This can result in long-lasting changes in cellular structure and function. The brain has receptors for many hormones, like the metabolic hormones insulin, insulin-like growth factor, ghrelin, leptin. These hormones are taken from blood and act to affect neuronal activity and certain aspects of neuronal structure. Hormones enter blood in response to stress and changes in biological clocks and travel to brain and other organs. In brain hormones alter production of gene products that participate in synaptic neurotransmission and affect structure of brain cells. Thus circuitry of brain and its capacity for neurotransmission are changed over a course of hours – days. This is how the brain adjusts to a changing environment. Although hormones are agents of protection and adaptation, stress and stress hormones like the glucocorticoid cortisol can also affect brain function like the ability to learn. Prolonged stress intereres with brain’s ability to function but can recover well. Female reproduction’s example: neurons in hypothalamus produce gonadotropin-releasing hormone (GnRH), a peptide that acts on cells in the pituitary. This caused follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to be released into blood for both males and females. In females they act on ovary to stimulate ovulation and promote release of ovarian hormones estradiol and progesterone. In males these hormones are carried to receptors on cells in testes where they promote spermatogenesis and release testosterone, an androgen, into blood. Testosterone, estrogen, progesterone are referred to as sex hormones. Increased levels of testosterone in males and estrogen in females act on pituitary to decrease release of FSH and LH. This increased level of sex hormones induce changes in cell structure and chemistry, leading to an increased capacity to engage in sexual behavior. Sex hormones also engage in other areas in brain, like attention, motor control, pain, mood, and memory. Sexual differences in brain is caused by sex hormones acting in fetal and early postnatal life, or by genes on either the X or Y chromosome. Differences between males and females include sizes of brain structures in the hypothalamus and arrangement of neurons in cortex and hippocampus. Sex differences can affect perceiving pain, dealing with stress, ways of solving cognitive problems, etc. Anatomical differences in heterosexual and homosexual men. Hormones and genes act early in life to shape brain in terms of sex-related differences in structure and function.

Gases and Other Unusual Neurotransmitters- nitric oxide and carbon monoxide. Don’t act like normal transmitters, not stored in structures like other transmitters. They’re made by enzymes as needed and released from neurons by diffusion. Instead of acting at receptor sites they simply diffuse into adjacent neurons and act upon chemical targets which may be enzymes. Exact functions for carbon monoxide haven’t been determined. Nitric oxide governs erection in penis and relaxation in intestine that contribute to normal movement of digestion. In brain it’s a major regulator of the intracellular messenger molecule cyclic GMP. When excess glutamate is released, as in stroke, neuronal damage afterwards can be attributed in part to nitric oxide.

Lipid Messengers- Brain also takes signals from lipids. Prostaglandins are a class of compounds made from lipids by an enzyme called cyclooxygenase. They have powerful effects even though they’re small and short-lived, like induction of fever and generation of pain in response to inflammation. Aspirin inhibits cyclooxygenase, reducing fever and pain. Another class of membrane-derived messenger is endocannabinoids, i.e. brain’s marijuana. They control release of neurotransmitters, usually by inhibiting them, and can also affect immune system and other cellular parameters still being discovered. Play role in control of behaviors. Increase in brain during stressful conditions.

Second Messengers- After action of neurotransmitter at receptor, biological communication within cells is triggered by substances called second messengers. Second messengers convey chemical message from neurotransmitter (first messenger) from cell membrane to cell’s internal biochemical machinery. Second messengers can endure from milliseconds to a lot of minutes and can be responsible for long term changes to nervous system. Example: ATP in cytoplasm of all cells. When norepinephrine binds its receptors to surface of neuron, activated receptor binds G protein on inside of membrane. Activated G protein causes enzyme adenylyl cyclase to convert ATP to cyclic adenosine monophosphate (cAMP), the second messenger. Instead of action on another messenger, cAMP exerts a variety of influences within cell, from changes in ion channels in membrane to changes in expression of genes in nucleus. Second messengers also thought to play role in manufacture and release of neurotransmitters, intracellular movements, and carbohydrate metabolism in cerebrum. Second messengers also involved in growth and development processes, and their direct effects on genetic material of cells could lead to long term alternations in cell functioning and changes in behavior.

Part 2– Developing Brain

Much of development of brain cells occurs in prenatal period. Many diseases considered now to be caused by pathways and connections in the brain not formed correctly earlier in life, i.e. schizophrenia. Genes important for brain development may play role in autism. Looking at how connections are made during development helps research for treatments after brain injury.

Journey of Nerve Cells:

Induction- During early stages of embryonic development, 3 layers form, endoderm, ectoderm, mesoderm. They undergo many interactions to become organ, skin, muscle, bone, or nerve tissue. Signaling molecules in mesoderm turn on certain gene cells and turn off others, triggering some ectoderm cells to become nerve tissue in neural induction. More signaling makes the nerve tissue into neurons and glia, then into subclasses of each type of cell. The other ectoderm cells that didn’t get signals become skin. Proximity of cells to signaling molecules largely determines fate, bc the concentration of these molecules spreads out and weakens as it moves away from its source. The signaling molecule sonic hedgehog is secreted from mesodermal tissue under developing spinal cord. Adjacent nerve cells converted to a special class of glia. Cell farther away are exposed to less sonic hedgehog so they become motor neurons. An even lower concentration promotes development of interneurons, which relay messages to other neurons, not muscles.

Migration-Journey of neurons to proper position in brain; 3-4 weeks after human baby is conceived. Ectoderm starts to thicken and build up along middle. Flat neural plate grows as cells continue to divide, with parallel ridges across surface. In a few days, ridges fold together into hollow neural tube. Top of tube thickens to form 3 bulges that form hindbrain, midbrain, and forebrain. Week 7- first signs of eyes and brain’s hemispheres appear. As neurons are produced they move from neural tube’s ventricular zone (inner surface) to border of marginal zone (outer surface). After neurons stop dividing they form intermediate zone, where they accumulate as brain develops.  The neurons then migrate to final destination with help of guiding mechanisms, including glia, projecting radially from intermediate zone to cortex. Cells that arrive earliest make deepest layer of cortex, while later-coming ones make outermost layer. Inhibitory interneurons, through another mechanism, migrate tangentially across brain. They are small neurons with short pathways usually found in the central nervous system. Alcohol, radiation, cocaine can affect migration and misplacement of cells, being a impetus for epilepsy and retardation.

Making Connections- Once neurons are in their final locations, they must make proper connections in the environment so that a particular function like hearing and sight can emerge. Neurons can become interconnected through the growth of dendrites or axons. Axons enable neurons at considerable distances to make connections. Growth cones, enlargements on axon’s tip, explore environment as they seek out their precise destinations. Special molecules help guiding growth cones. Some molecules lie on cells that growth cones contact while others are released from sources found near growth cone. Growth cones thus bear molecules that serve as receptors to environmental cues. Binding of particular signals with receptors tells growth cone whether to go forward, change direction, etc. These signaling molecules include proteins like netrin, semaphorin, and ephrin. These are usually families of related molecules. The first netrin was discovered in a worm and was used to guide neurons around the worm’s nerve ring. Once axons reach their targets they form connections with other cells at synapses. At synapse axon and dendrites talk. Connections must be highly specific for processing to occur properly; some specificity arises from mechanisms that guide each axon to proper target area. Additonal molecules mediate target recognition when axon chooses proper neuron and the proper target when axon reaches destination. Dendrites help initiate contact with axons and recruiting proteins to the “postsynaptic” side of the synapse. Synapse differentiates once contact has been made as axon and dendrite become specialized to send signals. Special molecules are transmitted between them to ensure that contact has been made properly and that sending and receiving specializations are matches precisely. This ensures that message can be sent quickly. Other molecules help with maturation of synapse as our bodies change. Defects in these molecules can make ppl be susceptible to disorders like autism. Loss of other molecules can underlie degradation of synapses that occurs during aging. Type of signals determines which neurotransmitter(s) that a neuron will use to talk to other cells. For moton neurons, its fixed, but for others it isn’t. Many researchers believe that signal to engage gene and final determination of chemical messengers that neuron produces is influenced by factors from the location of the synapse.

Myelination- Axons are wrapped by extensions of glia increases speed stuff can be sent by up to 100x. Depends on how sheath is wrapped. In between the myelin are gaps called nodes of Ranvier which are not covered in myelin. Saltatory conduction- transmitter jumps from node to node, responsible for fast travel of transmitters.

Paring Back- After growth, neural network is pared back to create more efficient system. Only half of the neurons generated in development survive to function in adulthood. Lots of neurons die in apoptosis, programmed death of cells initiated by the cells. Happens if neuron doesn’t get enough trophic factor. Nerve growth factor for example sustains sensory neurons. Apoptosis stays into adulthood; some degenerative diseases have cells kill selves this way. More connections formed at first, and those not receiving signals die.

Critical Periods- Paring down of connections occurs then. Critical experiences, like sensory, emotional, or movement, to mature properly. Neural circuits underlying behavior form. After critical period less connections but the remaining ones are stronger. Several critical periods- last is the 20s when frontal lobes finish developing. Deprivation during childhood is especially strong.

Plasticity- Experience-expectant: integration of environmental stimuli into normal patterns of development. Certain exposures are critical for neural maturity.

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