NSCI: NEW CONTENT
Anterograde amnesia
is the inability to form memories after onset of amnesia.
Effects of Hippocampal Lesions in Rats
- Normal rats go down each maze arm for food only once lesion: Not as efficient! - they go down the same arm more than once Normal and lesioned rats learn which arms are baited and avoid the rest. Lesioned still explore the baited arms inefficiently
Protein Kinase M Zeta PKM𝜻 is important for the maintenance of LTP
- Phosphorylates proteins that regulate AMPA receptor numbers - Phosphorylates proteins that regulate mRNA translation - Stays on long after Calcium - Translation of the kinase mRNA is activated by Calcium - ZIP specifically inhibits the kinase - ZIP zaps memories (Zip can erase LTP and memories established many days before the injection) zip disrupts performance in a Shock avoidance task & spatial memory 30 days after learning
Explain why phosphorylation of proteins as a long-term memory consolidation mechanism is problematic
- Phosphorylation is NOT permanent!! - Memories would be erased - Proteins aren't permanent - Other mechanisms needed for long-term consolidation -- Protein kinases -- Protein synthesis
Acquisition of a short-term memory
- Physical modification of brain caused by incoming sensory information - Modifying synaptic transmission between neurons (what did you have for dinner last night?)
Consolidation of long-term memory
- Requires new gene expression and protein synthesis (What did I have for dinner Oct 27 2005?)
Henry Molaison (Patient H.M.) 8cm length of medial temporal lobe bilaterally excised, including cortex, amygdala, and anterior 2/3 of hippocampus
- Severe anterograde amnesia resulted (inability to form new declarative memories!) - He did retain some memories of childhood. - Little to No memories for events just before surgery - Retrograde amnesia may have gone back decades - He did learn new floor plan of his home after the surgery and he was able to learn new tasks (new procedural memories) Medial temporal lobe is critical for memory consolidation but not for the retrieval of memories
Reasons we sleep
- Sleep as brain's way of disconnecting cortex from sensory input - By synchronizing oscillations from different regions, brain may bind together a single perceptual construction. - Sleep deprivation is devastating to proper functioning. - Purpose of sleep still unclear - Memory consolidation - The brain's lymphatic system is particularly active when we sleep and helps clear debris including beta amyloid (Mathew Walker) - For our brain, prevents cognitive impairment that comes with sleep deprivation
Effects of sleep deprivation
- cognitive impairment - increased irritability and emotional instability - Difficulty in concentrating - Episodes of disorientation - Sleep rebound (increased sleep time the next time you sleep)
key, real experiments that support the role of the suprachiasmatic nucleus (SCN) as a biological clock
- lesions of the SCN abolishes circadian rhythms in monkeys - SCN stimulation shifts circadian rhythms - transplantations of a new SCN into a lesioned animal can restore rhythms
The Electroencephalogram (EEG) - helps diagnose neurological conditions, such as epilepsy and sleep disorders, and for research
- noninvasive, painless - electrodes on scalp with low resistance connection - connected to banks of amplifiers and recording devices - voltage fluctuations measured (tens of microvolts) - electrode pairs: measure different brain regions Amplitude of the EEG signal a measure of synchronous activity of underlying neurons (larger amplitude) - measures generalized activity of MANY neurons of cerebral cortex
Hippocampus involved in various memory functions
1) Binds sensory information for memory consolidation 2) Supports spatial memory of location of objects of behavioral importance 3) Involved in storage of memories for some length of time
Evidence Implicating Medial Temporal Lobes in consolidation and storage of declarative memory:
1) Electrical stimulation of temporal lobes (complex sensations like recollections of past) 2) Recordings from temporal lobes (Halle Berry hippocampal neurons) 3) Temporal lobe amnesia in humans (HM) 4) Temporal lobe amnesia in animals (delayed non-match to sample)
Diffuse Modulatory Systems Critical to Control Sleep Diffuse modulatory systems drive thalamic neuron firing from rhythmic (sleep) to single spiking mode (awake)
1) Neurons MOST critical to control of sleep and wake are part of the diffuse modulatory neurotransmitter systems 2) 5-HT & NE neurons fire during & enhance wake; Different ACh neurons enhance REM sleep while others enhance awake states 3) Systems control the rhythmic firing of thalamus which controls EEG rhythms of cortex (slow rhythms of sleep in thalamus block sensory information from reaching the cortex! 4) Descending branches of these systems inhibit motor neurons during dreaming!
What experimental approaches would you use to understand the function of the hippocampus?
1) Temporal lobe amnesia in humans (HM) à Study human patients with hippocampal lesions 2) Electrical stimulation of temporal lobes à stimulate the hippocampus in patients undergoing neurosurgery and ask for them to report perceptions, etc. 3) Recordings from temporal lobes à record from neurons in the hippocampus while animals or humans perform behavioral tasks 4) Temporal lobe amnesia in animals (delayed non-match to sample) à lesion the hippocampus in animals
4 Stages of non-REM (fig 19.16)
1) Transitional sleep (few minutes and lightest) 2) Slightly deeper 5-15 min sleep spindles and K complex 3) Delta rhythms, deeper sleep 4) Deepest sleep! 20-40 min (slow large amplitude delta waves)
Four biological functions of sleep:
1. Energy conservation 2. Niche adaptation 3. Body restoration 4. Memory consolidation
5 Tips for a better night's sleep- Matthew Walker
1. Make it dark! (limit screen time, wear a mask, etc.) 2. Regularity (go to bed and wake up at the same time) 3. Keep it cool at night (65 to 68°F) 4. Don't stay in your bed awake (associative brain) 5. No Caffeine (post 2 pm) or night caps (alcohol)
Tri-synaptic Circuitry of the hippocampus
1.. Entorhinal cortex → dentate gyrus (perforant path) synapses 2. Dentate gyrus → CA3 (mossy fiber) synapses 3. CA3 → CA1 (Schaffer collateral) synapses
Human Narcolepsy results from the selective death of Hypocretin - containing neurons in most cases
25% of the general population has narcoleptic form of HLA gene, yet the majority don't develop narcolepsy. [Genes & Environmental Stressors] - Have frequent sleep attacks and excessive daytime sleepiness. - Do not go through SWS before REM sleep. May show cataplexy—a sudden loss of muscle tone, leading to collapse
Cooperativity
enough synapses active simultaneously to cause spatial summation and LTP at multiple synapses - because coactive synapses must cooperate to produce enough depolarization to cause LTP.
Reconsolidation
return of a memory trace to stable long-term storage, after recall Every time we retrieve a memory we alter it. Our emotions and experience at the time of that retrieval influence our memory of that event! Studies have shown that we can easily implant false memories in both animals and people.
Rhythmic activities of the brain
sleeping and walking, hibernation, breathing, walking, electrical rhythms of cerebral cortex
Associative learning
the association between two stimuli, or between a stimulus and a response - Classical conditioning (Pavlov): Pairing of unconditional stimulus with conditional stimulus US = food UR = salivation CS = bell CR = salivation
Consider how structural plasticity contributes to learning and memory
"Neurons that fire together wire together" Memory results from synaptic modifications. As certain connections are strengthened and others are lost.
Donald Hebb's message about the engram:
(1) It can be widely distributed among the connections that link the cells of an assembly (2) It can involve the same neurons that are involved in sensation and perception
Nonassociative learning
Change in behavioral response that occurs over time in response to a SINGLE stimulus
Increased firing rates in which of the following systems likely support the transition from sleep to wake? - all of these
- Acetylcholine (basal forebrain) - Norepinephrine (locus coeruleus) - Serotonin (raphe) - Histamine (midbrain)
Persistently Active Kinases- CaMKII
- Activated by Calcium - Autophosphorylating kinase - Keeps AMPA receptors phosphorylated: MAINTENANCE OF SYNAPTIC POTENTIATION - Molecular switch hypothesis: authophosphorylating kinase can store info at the synapse - Ten subunits activation of CaMKII is required for LTP! Molecular switch hypothesis - Autophosphorylation allows CaMKII to stay active even AFTER calcium levels drop. Can help store info at the synapse!
In instrumental conditioning—or operant conditioning—an association is made between Associate a response with a meaningful stimulus (Thorndike)
- Behavior (the instrumental response) - The consequences of the behavior (reward; punishment) animal is an active player ex. if the animal presses a lever it gets a reward (food).
Procedural Memory & The Striatum
- Different memory types involve different brain structures. - The striatum is involved in habit learning and procedural memory - Caudate nucleus + putamen = striatum - Key location in the motor loop --Input from frontal and parietal cortex --Output to thalamic nuclei and cortical areas involved in movement Lesions in striatum disrupt procedural memory (habit learning) —but not declarative memory
Multiple trace model of consolidation
- Engrams involve neocortex, but even old memories can also involve hippocampus. - Multiple memory traces - Each time a memory is retrieved, it occurs in new context with different sensory input creating a new memory trace!
Standard model of memory consolidation
- Information from neocortex areas associated with sensory systems sent to medial temporal lobe for processing - Synaptic consolidation, systems consolidation - Before systems consolidation, hippocampus required but after consolidation its not!
Synaptic Homeostasis • Unchecked synaptic plasticity could lead to unstable neuronal responses. - LTP is easier to induce in silent synapses
- LTP cannot go on forever, computer models suggest all synapses would be potentiated eventually and memory trace would be lost! - Homeostatic mechanisms needed to provide stability and keep synaptic weights within useful dynamic range - Metaplasticity rules of plasticity change with history of activity! (Synaptic modification threshold- NMDA receptor activation between that required for LTD and for LTP.) After high cortical activity & LTP→ NR2A levels increase now promoting LTD and making LTP harder to induce
molecular changes at the post synaptic level that can produce LTP
- More AMPA receptors expressed - More AMPA receptors moved to post synapse and on edges of synpatic cleft - AMPA receptors phosphorylated → stay open longer → more depolarization from the same amount of glutamate release - More PSD95- bigger "egg carton" to hold more "eggs" (i.e. AMPA receptors) - More AMPA receptors with GluR1 subunit - BDNF involved in growth, dendrite makes branches, spines increase, dendritic branching - More NMDA receptors made
Fear Conditioning (learned fear)
- Neurons in the central amygdala respond to the shock related tone! - Amygdala lesions eliminate the learned visceral responses (blood pressure, heart rate)
Memory reactivation during SWS Sleep Replay of an awake experience may result in memory consolidation
- Neurons in the visual cortex and the hippocampus fire in a sequential pattern when the rats run a figure 8 maze - During SWS after running the maze, the temporal & spatial firing sequence is maintained in the cortex and in the hippocampus [Coordinated memory replay in the visual cortex and hippocampus during sleep] - Acetylcholine system is important for this consolidation during SWS! -Individuals that were re-exposed to the odor during SWS performed better at retrieval [Odor cues during slow-wave sleep prompt declarative memory consolidation]
molecular changes at the pre synaptic level that can produce LTP
- Nitric Oxide - Decreased Threshold for AP firing - Increased release of neurotransmitter (increased number of loaded vesicles primed for release) - Axon expansion - Release of transmitter from additional sites
LTP induction requires AMPA and NMDA receptors (Glutamate receptors- ligand gated ion channel)
AMPA: Sodium (not calcium) flows through the channel when open - Glutamate alone is sufficient to open the channel - No Mg++ - Responds to the drug AMPA - agonist NMDA: Glutamate alone is insufficient to open the channel - Mg++ under resting conditions blocks the channel pore - Depolarization and Glutamate required to open the channel - Na+ and calcium flow through the channel (calcium acts as a second messenger -> CaMKII -> CREB -> transcription and synaptic changes-BDNF dendritic branching) - Responds to NMDA
Categorization of rhythms based on frequency
Beta: 15-30 Hz, activated or attentive cortex low amplitude Alpha: 8-13 Hz, quiet, waking state Theta: 4-7 Hz, some sleep and waking states Delta: less than 4 Hz, deep sleep. (seen in stage 3 and 4 sleep) Spindles, ripples
NMDA Receptors as "coincidence detectors"
Co-occurrence of activity in pre- and post- synaptic neurons is detected by NMDA receptors and required for LTP.
Neural Mechanisms of Sleep
REM on cells = cholinergic cells of the pons. REM off cells = LC and raphe firing increases just before the end of REM sleep and go back down (fig 19.21) Some cholinergic (ACh) neurons fire to enhance REM events
LTP Expression Mechanisms
Dendritic Depolarization + Glutamate -> NMDA receptor opening -> Calcium entry -> CaMKII -> CREB -> Gene expression & long lasting changes
Diseases with links to lack of sleep
Diabetes, Cardiovascular Disease, Obesity, Depression, Anxiety Disorders, Alzheimer's disease
REM sleep state of brain
EEG: low voltage, fast Sensation: vivid, internally generated Thought: vivid, logical, bizarre Movement: paralysis, movement commanded by the brain but not carried out
Hypothetical Stages of Memory
Encoding - Acquisition: registers inputs; sensory analysis - Consolidation: creates a stronger representation over time Storage - Represents the record of the information Retrieval - Utilizes stored information to create a conscious representation or to execute a learned behavior Reconsolidation - Reactivation of the memory makes it sensitive to change as when first formed
Memory trace "The physical representation or location of a memory; also known as an engram"
Ensembles of neurons are thought to serve as engrams
Declarative memory (explicit) (medial temporal lobe, diencephalon)
Facts and events - things you know that you can tell others (hippocampus dependent) [episodic- first day of school; semantic- capital of france]
Define learning and memory
Learning is the acquisition of new knowledge or skills. Memory is the retention of learned information.
Evaluate how striatal and hippocampal lesions impact procedural memory.
Lesions in striatum disrupt procedural memory (habit learning) —but not declarative memory Standard radial arm maze performance (declarative memory) depends on hippocampus Modified radial arm maze performance (performance memory) depends on striatum. - Damaged hippocampal system: degraded performance on standard maze task - Damaged striatum: impaired performance of the modified task
The Amygdala and Sleep Deprivation
No sleep... Amygdala heightened response to negative stimuli Reduces the ability of pre-frontal cortex to suppress activity in amygdala
CREB1 - promotes transcription (needs to be phosphorylated) CREB 2 - blocks transcription
OVERexpress CREB 1→ "photographic" memory, learn a task in a single training rather than many (drosophila evidence) Also evidence in Aplysia and mice (spatial memory) OVERexpress CREB 2 → blocks transcription (repressed gene expression) → block memory consolidation and performance in simple memory task
CREB & protein synthesis
Protein synthesis inhibitors block LTM consolidation. New protein synthesis is important during period of memory consolidation (STM → LTM) CREB: cyclic AMP response element binding protein (is a transcription factor! regulates gene expression) - Functions to regulate expression of neighboring genes - Tully and Yin- CREB regulates gene expression required for memory consolidation.
Spatial Memory & Place Cells
Place cells fire when an animal is in a specific place. They are dynamic! When you remove the partition the place field moves.
Nondeclarative memory (implicit)
Procedural memory—motor skills, habits - things you know that you can show by doing (hippocampus interdependent)
Memory contamination and the "misinformation effect"
Profound implications for eye witness testimony and treatment of stress associated with unpleasant memories (PTSD)
Rat experiments
Reactivating a peaceful memory (optogenetics) of a blue box while being shocked changes the memory of the blue box to a fearful one!
Describe the process of distributed memory storage
There is a unique pattern or ratio of activity in the three neurons for a face. The memory is distributed and not in just one synapse - memory is represented by a distributed pattern of activity across all neurons in the cortical network (a memory engram)
Sleep: a readily reversible state of reduced responsiveness to, and interaction with, the environment
Universal among higher vertebrates - one third of our lives spent in sleep state TWO stages - REM - Non REM (Stages 1-4) repeating cycle about every 90 min these cycles are examples of ultradian rhythms, which have faster periods than circadian rhythms
Partial activation of a memory trace may stimulate memory!
When I make my grandmothers caramel cake, the smell of it triggers an entire memory of her and her kitchen for me. Its not that the smell of caramel cake activates all the neurons representing the memory But rather activation of just part of the engram (olfactory sensory neurons in the cortex) triggers activation of the entire memory trace
Weak stimulation of input 1 synapses induces LTP that would normally fade, but...
When followed an hour later by strong stimulation of input 2 synapse, the wave of new proteins can be captured by synapses tagged by the weak stimulation of input 1 - Persistently activated kinases may be involved in this "synaptic tagging"
INPUT SPECIFICITY -ONLY active inputs show the synaptic plasticity; before the HFS we measure the baseline EPSP size AFTER HFS the size of the EPSPs increases!
Without tetanus, there is no LTP for input 2 → input specificity. ONLY the synapse with high activity (tetanus of input 1) will produce LTP
What part of the nervous system generates the fluctuations and oscillations of an EEG?
an EEG measures voltages generated by the currents that flow during synaptic excitation of the dendrites of many pyramidal neurons in the cerebral cortex
Non-REM sleep state of brain
high synchrony (high EEG amplitude), low frequency rhythms - delta rhythms EEG: high voltage, slow Sensation: dull or absent Thought: logical, repetitive Movement: occasional, involuntary
LTD in CA1 LTD: long lasting decrease in the strength of a synapse based on recent patterns of neuronal activity
how to induce LTD- low frequency stimulation how can both LTD & LTP induction require NMDA receptors & calcium entry? All about concentration- low levels of calcium result in LTD Synaptic transmission occurring at the same time as weak or modest depolarization of the postsynaptic neuron causes LTD - NMDA receptor dependent - when weak depolarization of postsynaptic neuron only a little calcium comes through
Sensitization
is a form of learning where your response intensifies to a stimulus, even when previously that stimulus evoked little or no reaction ex. You live in a busy city where horns honk all the time and don't get much reaction out of you. A few hours ago you were in a car accident and now any horn honk startles you tremendously
habituation
is learning to ignore a stimulus that lacks meaning (in a big city you quickly become habituated to sound of cars going by, noise of the city, etc.)
Retrograde amnesia
is the loss of memories formed before onset of amnesia and is not uncommon after brain trauma.
Long term potentiation (LTP) researched cause: easy to dissect out simplified circuit; can be kept alive ASCF and bubbling oxygen and then sliced into brain slices for electrophysiology; known role in learning and memory from lesion in HM and rodent studies
long lasting increase in the strength of a synapse based on recent patterns of neuronal activity - can last for many months in freely moving animals (at least a year)
Awake state of brain
low synchrony (low amplitude), high frequency rhythms - beta and gamma rhythms dominate EEG: low voltage, fast Sensation: vivid, externally generated Thought: logical, progressive Movement: continuous, voluntary
Later studies of patient H.M revealed his retrograde amnesia went back decades. Click on the model of memory consolidation supported by this evidence.
multiple trace model of consolidation
You are testing memory in Drosophila. You overexpress CREB-2. What is the likely consequence?
you've repressed gene expression and blocked the mutant flies memory consolidation
Characteristics of REM sleep
• Active, hallucinating brain in paralyzed body • Atonia (loss of muscle tone) • Beta and gamma rhythms • Fast, low amplitude EEG • Paradoxical sleep • Rapid eye movements • Sympathetic activation • Vivid dreaming
Sleep promoting factors: Caffeine (Adenosine receptor antagonist)
• Adenosine builds up the longer you are awake, builds sleep pressure • Caffeine Blocks sleep pressure • But once caffeine wears off, the adenosine has continued to build and sleepiness returns with a vengeance • Adenosine inhibits Ach, NE and 5HT systems
More evidence linking LTP, LTD & memory...
• Avoidance learning results in CA1 LTP - Novel environment causes LTD • NMDA receptor inhibition prevents avoidance learning - APV = NMDA receptor antagonist • NMDA receptor blocking prevents morris water maze learning • CaMKII KOs show hippocampal LTP & memory deficits • NMDAR KO in CA1 specifically- LTP, LTD & water maze learning deficits • LTP and LTD can be induced in human IT slices
Golden hamsters are perfectionists of circadian timing
• Circadian rhythms are disrupted in animals with SCN lesions under dim light conditions. • Endogenous rhythm disappears.
Characteristics of non-REM sleep
• Four stages • Idling brain in a movable body • Delta Rhythms • Slow, large amplitude EEG • K complex • Period for rest • Reduced Muscle tension • Parasympathetic activation • Sleep spindle
Zeitgebers: Any environmental cue, such as the light-dark cycle, which signals the passage of time.
• German for "time givers" • Environmental time cues • For mammals: primarily light-dark cycle The clocks that time circadian rhythms are in the brain, calibrated by the sun via the visual system, and they profoundly influence our health and well-being.
PTSD Implications:Drug Targeting Gene Expression Regulation Erases Fear Memories
• HDAC2 is a master regulator of neuronal genes • required for fear conditioning memory in mice • Extinction therapy - playing the tone with no shock. Similar to exposure therapy used in humans with PTSD. BUT it doesn't fully erase the memory • 30 days later- extinction plus an HDAC2 inhibitor can wipe out the memory!
The Hippocampus: "What happened, where"
• HM studies -> declarative memory consolidation • Hippocampal rat lesion studies, rat neuron recordings (place cells) & human imaging studies -> spatial memory • Recording neurons in humans -> selectivity for people (Halle Berry) and objects (Statue of Liberty) • Hippocampal lesions & recordings demonstrate its role in odor discrimination -> forming associations between sensory stimuli (like odor)
Suprachiasmatic Nucleus (SCN)
• Intact SCN produces rhythmic message: SCN cell firing rate varies with circadian rhythm. • Retinal input necessary to entrain sleep cycles to night
Research perspectives implicate LTP in memory:
• LTP is widely studied because it involves synaptic changes that evidence suggests are the basis of memory storage pharmacological treatments that block LTP also impair learning - Mice that overexpress NMDA receptors have enhanced LTP and better memory
Lifestyle factors can help reduce cognitive decline:
• Living in a favorable environment • Involvement in complex and intellectually stimulating activities • Exercise Rat in complex environment- shows increase in number of dendritic spines by about 25% - Environmental enrichment (EE) has been widely used as a means to enhance brain plasticity mechanisms
Delayed non-match to sample
• Monkey faces a table with small wells on the surface, first sees the well with one object covering the well • Monkey is trained to remove the object and find a food reward beneath • After the monkey gets the reward a screen is used to prevent the monkey from seeing the table for some period of time (delay interval) • After the delay interval, the monkey gets to see the table again but now there are two objects on it (one is the same as before and one is new) • In DNMS, the monkey has to displace the NEW object to get the reward Similar to HM, amnesia was anterograde, declarative rather than procedural, working memory was intact, and consolidation was severely impaired!
Sleep patterns change with older age
• Overall reduction in sleep & earlier wake up times • Reductions in the proportion of REM sleep (20%), especially relative to early stages in life (childhood & infancy 50%) • By age 40 to 50 we can lose as much as 50% of our deep, non-rem sleep! And by age 70 it can be as much as 90%. Not good and linked to diseases like Alzheimer's Disease and deficits in learning and memory • A lot of sleep disruptions (pain, bathroom trips, etc.) are seen in old age. You don't go to sleep and stay asleep anymore. • PROTECTING YOUR SLEEP IS PROTECTING THE HEALTH OF YOUR MIND AND BODY! (remember from the podcast shorter sleep = shorter life) - in the elderly: severe reduction in stage 3 of sleep and frequent awakenings
Hippocampus in Navigation
• PET imaging in human brain related to spatial navigation of a virtual town London taxi drivers - interesting correlation between the size of the hippocampus and time spent as a taxi driver 2003-Direct recording from neurons in MTL reveal place cells
Acting Out a Dream
• Projections to motor neurons in the spinal cord inhibit movement during sleep • Small lesions ventral to the locus coeruleus prevent the loss of muscle tone during REM sleep. • Cats with such lesions seem to act out their dreams. • REM sleep disorder is commonly observed in Parkinson's Disease and often begins before diagnosis • Locus coeruleus neurons degenerate very early in Parkinson's Disease
Learning Morris water maze requires the hippocampus. (how lesions of the hippocampus affect spatial memory)
• Rats with bilateral lesions of hippocampus do not remember the platform or learn to search for it efficiently
Sleep promoting factors: Melatonin
• Released when the environment darkens • Release inhibited by light! • Like the organizer of a race, helps get all of the players ready and then fires the starter pistol. (initiating sleep) • Most helpful for jet lag or older adults with low secretion levels
Infant sleep is characterized by: Mammals sleep more during infancy than in adulthood.
• Shorter sleep cycles • More REM sleep—50%, which may provide essential stimulation to the developing nervous system Babies sleep a lot early in life but they are not entrained yet to our light dark cycle
Disrupted Sleep- a risk factor for Alzheimer's disease & an early symptom
• Tau & Aβ accumulate in Alzheimer's disease • Much of the brain's self-cleaning of these proteins by its lymphatic system occurs during sleep. 1st Evidence for human brain lymphatic system in 2017!! • Disrupted sleep = increased tau earlier in life • Sleep patterns could be use as a biomarker for Alzheimer's risk, and perhaps sleep interventions may delay its onset
Brain Transplants Show that the SCN Contains a Clock
• Transplant studies show that the endogenous period is generated in the SCN. • Hamsters with SCN lesions received a SCN tissue transplant from hamsters with a short period (a genetic mutation called tau). • Circadian rhythms were restored but matched the shorter period of the donor
