Source: MCB C61, UC Berkeley
Tags: cannabis, cannabinoids, THC, CBD, endocannabinoids, anandamide, 2-AG, retrograde signalling, neuroplasticity, human genome, neural tube, stem cells, neurogenesis, synaptogenesis, growth cone, cytoskeleton, microtubules, chemoaffinity hypothesis, Roger Sperry, neurotrophins, pruning, hippocampus, Marian Diamond, chemotaxis, phototaxis, naive realism, electromagnetic spectrum, electroreception, magnetic field, Karl von Frisch
This section covers the endocannabinoid system (how cannabis works in the brain), the fundamentals of neurodevelopment from embryonic stem cells through to adult neurogenesis, and the opening concepts of sensory perception. The sensory material spans bacterial chemotaxis through to the full range of animal senses, including vision, hearing, electroreception, and magnetoreception, all built around the idea that perception is a constructed representation of reality, not reality itself.
Cannabis / cannabinoids
Cannabis is an ancient medicinal plant with properties including analgesia, anti-inflammatory, muscle relaxant, reduced intraocular pressure, antiseizure, antiemetic, and sedation. Cannabinoids are the specific compounds in cannabis responsible for these effects. Classified as Schedule 1 federally, though state laws vary.
THC (tetrahydrocannabinol)
The primary psychoactive cannabinoid in cannabis. Discovered by Raphael Mechoulam in 1964.
CBD (cannabidiol)
A cannabinoid with medicinal properties but without the psychoactive effects of THC.
Raphael Mechoulam
Discovered THC (1964), endocannabinoids, and cannabinoid receptors. Nearly all cannabis research stems from his work.
Endocannabinoids
Molecules produced naturally in the body that function as neurotransmitters at cannabinoid (CB) receptors. They are retrograde neurotransmitters.
Anandamide
The first discovered endocannabinoid. An agonist at CB receptors.
2-AG (2-arachidonoylglycerol)
Another endogenous agonist at CB receptors.
Cannabinoid receptors
GPCRs found in the brain that respond to both cannabinoids and endocannabinoids. They use retrograde signalling.
Retrograde signal
A signal that travels in the opposite direction to conventional neurotransmission, going from dendrites back to axon terminals. Capable of creating changes in synapse strength, which is central to neuroplasticity.
Neuroplasticity
The principle that the strength and connectivity of synapses is dynamic and always changing. Closely linked to learning and development because neural pathways can be strengthened through repetition.
Human genome
23 chromosomes (haploid), approximately 3 billion base pairs, about 21,000 distinct protein-coding genes. Only about 3% of the genome is translated into proteins; roughly 85% is transcribed into mRNA.
Neural tube
Forms from folded cells at approximately 3 weeks of embryonic development. The entire central nervous system develops from this structure.
Transcription factors
Proteins that bind to DNA regions and regulate gene readout. They are the regulators of cell differentiation.
Neurogenesis
The creation of new neurons.
Gliogenesis
The creation of new glial cells.
Synaptogenesis
The formation of synapses between neurons. Occurs alongside neurogenesis, gliogenesis, and the branching of axons and dendrites.
Growth cone
The tip of a growing axon, possessing mechanisms of sensitivity, motility, and guidance. Progresses via the extension of filopodia.
Cytoskeleton
Composed of ordered arrays of protein polymers: microtubules (made of alternating alpha and beta tubulin) and microfilaments (long polymers of actin).
Roger Sperry
Cut the optic nerve of a frog, rotated the eye, and observed that the regrown nerve still mapped to its original orientation (the frog saw upside down and backwards). This led to the chemoaffinity hypothesis.
Chemoaffinity hypothesis
Neurons use specific chemical signals to guide their wiring (migration and synaptogenesis) during development.
Neurotrophins / nerve growth factors
Proteins important for cell growth and development. NGF was the first neurotrophin discovered; others include BDNF and GDNF.
Guidance factors
Proteins such as ephrin, netrin, neuropilin, plexin, semaphorin, Slit, and Robo that direct cell growth toward or away from contact points.
Pruning (synaptic pruning)
The elimination of synapses that are not used. After birth, far more synaptic connections form than will be retained.
Hippocampus
A bilateral structure beneath the temporal lobe surface, shaped like a seahorse. Plays a pivotal role in memory formation and stabilisation. The primary site where adult neurogenesis has been recorded, with possibly up to 1,400 new neurons added per day.
Marian Diamond
A pioneering UC Berkeley professor whose team published the first evidence that the brain can change with experience (confirming plasticity). Her research on Einstein's brain advanced understanding of the roles of glial cells.
Chemotaxis
Movement of a cell or organism in response to a chemical gradient. In E. coli, bacteria alternate between runs (straight swimming, flagella bundled) and tumbles (random reorientation, flagella apart). Nutrient chemicals reduce tumble frequency, biasing movement toward the nutrient source.
Phototaxis
Movement of an entire organism toward light.
Phototropism
Growth of an organism toward light (e.g. a plant bending toward a window).
Phycomyces
A fungus that does not photosynthesise but has extreme light sensitivity. Uses light to direct growth of its sporangiophores (fruiting bodies) so spores disperse in open terrain.
Naive realism
The notion that what we perceive is identical to what exists in the world. Easily disproven by optical illusions. All perception involves transformation of sensory signals by the nervous system, resulting in a constructed representation.
Ontology
The study of the nature of reality: what is it that exists?
Cannabinoid receptors are GPCRs found throughout the brain
Endocannabinoids (anandamide, 2-AG) are the body's own agonists at these receptors
Endocannabinoids are retrograde neurotransmitters: they carry signals from dendrites back to axon terminals
This retrograde signalling can alter synapse strength, which is a mechanism of neuroplasticity
THC and CBD are the primary phytocannabinoids responsible for cannabis's psychoactive and medicinal properties
Nearly all scientific understanding of this system traces back to Raphael Mechoulam's work beginning in 1964
The human genome:
23 chromosomes (haploid), ~3 billion base pairs, ~21,000 protein-coding genes
Only ~3% is translated into functional proteins
~85% is transcribed into mRNA (most of the genome is transcribed but not translated)
Embryonic development of the nervous system:
At 3 weeks, the neural tube forms from folded cells; the entire CNS develops from it
Brain growth accelerates by the third month after conception
Gyri and sulci form in the last two months before birth as expanding neuron and glial cell populations increase brain volume
Stem cells differentiate into nervous system progenitor cells, which become neurons and glia
Transcription factors regulate which genes are read out and thus control cell differentiation
Key developmental processes:
Neurogenesis, gliogenesis, axon/dendrite branching, cell migration, and synaptogenesis all occur together
Growth cones at axon tips use filopodia to navigate; their guidance depends on chemical signals
The cytoskeleton (microtubules of tubulin, microfilaments of actin) provides structural support and motility
Chemoaffinity hypothesis (Sperry): neurons use specific chemical signals to guide wiring during development
Neurotrophins (NGF, BDNF, GDNF) promote cell growth; guidance factors (ephrin, netrin, semaphorin, Slit, Robo, etc.) direct axon pathfinding
After birth:
Vast numbers of new synaptic connections form in the cerebral cortex, more than will ultimately be retained
Synaptic pruning eliminates unused synapses
Even in adults, neurogenesis occurs, particularly in the hippocampus (up to ~1,400 new neurons per day)
Naive realism is the default human assumption that perception = reality. The café wall illusion and similar demos disprove this. All perception is a transformed and constructed representation: incoming neural signals interact with vast networks of established cortical activity. What we perceive is sufficient for survival and reproduction, but it is not a direct window onto the world.
E. coli swims via alternating runs (straight, flagella bundled) and tumbles (random, flagella apart), together called a random walk
Chemotaxis: nutrient chemicals interact with receptor proteins on the bacterial membrane, reducing tumbles and biasing movement toward the nutrient
Phototaxis (organism moves toward light) and phototropism (organism grows toward light) increase exposure to light for photosynthetic organisms, or help non-photosynthetic organisms like Phycomyces disperse spores
Human vision responds to a narrow band (~400–700 nm) of the electromagnetic spectrum
Ultraviolet: higher energy than visible light; seen by insects, birds, and some other animals
Infrared: lower energy than visible light; detected by pit vipers and rattlesnakes via pit organs positioned near the nostrils, enabling prey location in total darkness
Many flowers have nectar guides visible only in UV light, attracting bees and other pollinators (honeyguides)
Light polarisation and navigation:
Sunlight vibrates at all polarisation angles; atmospheric scattering produces polarisation patterns across the sky
Humans cannot detect polarisation without a filter (discovered by Karl von Frisch)
Many animals (birds, fish, sea turtles, honeybees) detect the geomagnetic field and use it for navigation
Pigeons are the best-studied navigators; small magnets interfere with their homing ability
Karl von Frisch (1886–1982):
Demonstrated that honeybees have colour vision (including UV sensitivity), against prevailing belief
Nobel Prize for Physiology or Medicine, 1973
Human hearing: 20 to 20,000 Hz
Infrasound (<20 Hz): generated and heard by elephants for communication
Ultrasound (>20,000 Hz): dogs and cats hear up to ~40,000 Hz; echolocation by bats, dolphins, and whales uses frequencies above 100,000 Hz
High-frequency sound has short wavelengths, permitting fine spatial discrimination (e.g. a bat locating a tiny insect)
Electroreception: detection of bioelectric fields generated by living organisms
Passive electroreception: sensing weak fields from other animals (e.g. sharks using ampullae of Lorenzini to detect prey; also used by platypus and echidna)
Active electroreception: generating one's own oscillating electric field and detecting distortions caused by nearby objects or animals (e.g. electric fish in the Amazon and South Africa)
Electric fish use species-specific field frequencies for communication and environmental detection
Earth's geomagnetic field is generated by movement of magnetic atoms in the planet's molten interior
Field intensity varies (strongest at poles, weakest at equator); field direction becomes more steeply inclined near the poles
Animals use multiple cues for navigation: sun position, odours, sounds, visual landmarks, and the geomagnetic field
⚠️ Endocannabinoids are retrograde neurotransmitters (dendrite → axon terminal). This is the opposite direction from conventional neurotransmission. CB receptors are GPCRs.
⚠️ Only ~3% of the human genome codes for proteins, but ~85% is transcribed. Know the difference between transcription and translation percentages.
⚠️ Synaptic pruning is the removal of unused synapses, not unused neurons. After birth, more connections form than are retained.
⚠️ The hippocampus is the key site for adult neurogenesis. Know its location (beneath the temporal lobe) and its role in memory.
⚠️ Naive realism is easily disproven. Perception is a constructed representation, not a direct readout of reality.
⚠️ Know the difference between passive and active electroreception: passive detects other organisms' fields; active generates and reads distortions in one's own field.
Q: What is retrograde signalling, and why is it important for the endocannabinoid system?
A: Retrograde signalling carries information from dendrites back to axon terminals, opposite to normal neurotransmission. Endocannabinoids use this mechanism to modulate synapse strength, which underlies neuroplasticity.
Q: What percentage of the human genome is translated into proteins, and what percentage is transcribed?
A: About 3% is translated into functional proteins. About 85% is transcribed into mRNA.
Q: What is the chemoaffinity hypothesis, and who proposed it?
A: Roger Sperry proposed that neurons use specific chemical signals to guide their wiring during development. He demonstrated this by cutting and rotating a frog's optic nerve and observing that regenerated connections followed original chemical cues, not the new orientation.
Q: How does chemotaxis work in E. coli?
A: E. coli alternates between straight runs and random tumbles. When nutrient chemicals interact with receptor proteins on the bacterial membrane, tumble frequency decreases, biasing the bacterium's movement toward the nutrient source.
Q: What is the difference between phototaxis and phototropism?
A: Phototaxis is movement of the entire organism toward light. Phototropism is growth (bending) toward light.
Q: How do pit vipers detect prey in complete darkness?
A: They use infrared-sensing pit organs positioned below their eyes and near their nostrils. These organs detect infrared radiation emitted by warm-blooded prey, functioning similarly to how eyes detect visible light.
Q: What is naive realism?
A: The assumption that what we perceive is identical to what exists in the world. It is easily disproven by illusions and by the fact that all perception involves transformation and construction by the nervous system.
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