Senior Seminar Oral Final Exam Topics

medulla

life sustaining processes

pons

wakefulness, sleep

cerebellum

balance, coordination, rhythm, learning, timing of movements

VTA

dopamine neurons start here, bottom part of tegmentum

substantia nigra

movement

frontal lobe

risk taking, planning, decision making, motorp

parietal lobe

sensory

temporal lobe

auditory, memory

amygdala

emotion processing, specifically fear, part of limbic system

thalamus

sensory information processing connection, relays to areas of cortex

hypothalamus

tells pituitary gland to release hormones; four f’s: fleeing, feeing, fighting, fucking

caudate, basal ganglia, putamen, global pallidus

movement and procedural learning

hippocampus

memory and learning

GABA

reduces anxiety, alcohol inhibits this, inhibitory NT, metqabolic receptors

glutamate

excitatory, learning and memory

acetylcholine

excitatory, memory adn learning, specifically alz disease

serotonin

mood regulation, psychedelics work here, MDMA was binding site in octopi here, sleep, reuptake and mao clears synapse

dopamine

reward, gambling, VTA, makes norepi, parkinson’s disease (decrease in dopamine), gambling

norepinephrine and epinephrine

SNS activation, memory, yell at us, transporter does reuptake

fast scan cyclic volammetry

electrochemical, looks at release and uptake of NTs, measure amount of specific NT in brain region

fiber photometry

optical fiber that delivers light to deep portions of brain, look at brain changes

viral vector

modified virus used as delivery vehicle to get genetic materials into cells

ELISA

creates signal in tissue/fluid sample detecting specific protein

cFOS

protein acting as marker for cell/neuronal activities, each time cesl fire, gives off cFOS activity

Tsai et al: Dopaminergic neurons is sufficient for behavioral conditioning

Using rats, researchers studied how optogenetically stimulating dopamine neurons in the VTA phasically (short bursts) could condition rats to spend more time in the chamber where they received the dopamine firing.

This built on the literature which previously suggested that you needed steady firing. Prev lit also said sitm of medial forebrain bundle is highly reinforcing in rats

Braak et al: Stages of the pathologic process in alzheimer’s disease: age categories from 1 to 100 years

Previous literature showed that AD tau changes begin decades before symptoms. This study created stages of AD progression based on tau tangles/behavior in human brains post mortem. 

Stage a-c: locus coeruleus/subcortical regions

Stages 1-6: Neurofibrillary Tangles Stage

Stage 1: Transentorhinal Cortex and Entorhinal Cortex (in Medial Temporal Lobe)

Stage 2: Hippocampus

Stage 3: Temporal lobe, amygdala

Stage 4: Insular and Basal frontal areas, limbic regions

Stage 5: Prefrontal Cortex and Neocortex

Stage 6: Premotor, primary motor areas, frontal, occipital parietal lobes

We saw stages a-c almost 80% of the time in 10-20 year olds, starts way earlier and affects way more than we thought

Rorabaugh et al: Chemogenetic locus coeruleus activation restores reversal learning in a rat model of Alzheimer’s disease

TgF344-AD genetically modified rat-shows alzheimer’s progression similar to humans

Initially sucked at morris water maze; used designer drugs to activate locus coeruleus, which led rats who were impaired initially to do as well as WT rats on reverse learning in morris water maze

Roh et al: Potential role of orexin and sleep modulation in the pathogenesis of alzheimer’s disease

Sleep can play a role in development of AD, and orexin neurons regulate the sleep/wake cycle. Using orexin knockout mice which typically develop AD pathology within 2 months, gave injections of lentivirus containing orexin into hipp. Sleep deprived some orexin KO mice and saw an increase in AB plaque pathology. More sleep led to less amyloid B plaques with orexin KO mice. Restoring orexin in hippocampus increased wakefulness and AB pathology.

Swift et al: Sex differences within sleep in gonadally intact rats

Looked at EEG readings of sleep in rats between females with estrus and males. Females in proestrus had high wake periods, and low nrem and rem. Had less sleep, but more intense sleep waves when asleep. Females in estrus had similar but less intense spiky patterns. Those in diestrus and metestrus had similar steady rates. Sleep spindles density increased in proestrus and estrus.

Roybal, K. et al: Mania-like behavior induced by disruption of CLOCK

CLOCK is a circadian rhythm protein. Used mice with mutant CLOCK, who presented with behavioral effects of mania (increased activity and reaction to rewarding stimuli/drugs, decreased sleep, anxiety, and depression). CLOCK mutant mice had more sensitivity to stim of median forebrain bundle/needed less stimuli to create a pattern of response. When put CLOCK back into mutant mice’s VTA, CLOCK effects were restored.

Vadnie, C. A. et al. The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice.

The suprachiasmatic nucleus (SCN) regulates sleep, and disruption leads to anxiety and depression. Electric recordings of movement and breathing were measured in genetically modified mice, then did optogenetic stimulation. They found that those who received stimulation changed and decreased amplitude of rhythm. Unpredictable dark phases decreased amplitude and decreased stability. Chronic stimulation led to decreased amplitude and anxiety symptoms. Amplitude was change in homecage behavior changed to baseline.

Alia-Klein, N. et al. Brain Monoamine Oxidase A Activity Predicts Trait Aggression

MAOA breaks down NTs and if you block it you get aggression. Trait aggression (physical assault) has been seen in MAOA KO pups. Lower MAOA can lead to trait aggression. Using PET scans for MAOA and multidimensional personality questionnaires, researchers found that MAOA in brain inversely correlates with trait aggression in MPQ. Lower MAOA in cortical and subcortical regions led to increased aggression.

Modi, M. E. et al. Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole.

The Melanocortin system regulates food and stress but interacts with systems that regulate social behavior and NTs. Activating MC4R in uterus of prairie voles led to enhanced social bonding in adulthood. Adult prairie and meadow voles were used in the study, and injections were given of a vehicle or peptide agonists (MT1, MT2, and MC4R). Then, they did a partner preference test. MCR agonist administration led to increased partner preference in prairie voles, and a high dose of MT2 and low of MC4R led to enhanced partner preferences in females. When blocked oxytocin receptors in NAc, MC2’s effect disappeared. Increased OT neurons after MT2 injections. meadow voles are asocial.

Edsinger, E. & Dölen, G. A Conserved Role for Serotonergic Neurotransmission in Mediating Social Behavior in Octopus

Octopi’s SERT (serotonin transporter gene) SLC64A was found to be a binding site in octopi over evolution, a place MDMA also binds. Using a three chambered social assay, researchers saw that octopi were like generally asocial. When novel octopus was female, both M/F octopi spent more time in the chamber with an octopus than the center one they were initially placed in. Spent more time in novel object chamber if novel octopus was a male. If novel octopus was male, time spent with novel object increased and time spent in chamber with novel octopus decreased compared to females. Then once given MDMA bath, more time in object chamber in pre trial, more time in social other chamber when post trial; time spent with social octopus sig increased after MDMA

Tyler, R. E. et al. Predator odor (TMT) exposure potentiates interoceptive sensitivity to alcohol and increases GABAergic gene expression in the anterior insular cortex and nucleus accumbens in male rats

GABA in NAc and anterior insular cortex is involved in subjective effects of alcohol. Increased alcohol drinking after predatory odors. Using male rats, researchers used a 2 lever drug discrimination task for alcohol or water. Then, gave 15 minute exposure to fox TMT (stressor), and looked at alcohol response curve over next two weeks. With TMT exposure there was more activity in the NAc and insular cortex in alcohol naive rats. It also increased GAD-1 activity (produces GABA) in AIC, and GAT-1 (gaba transporter) in NAC. Rats had different responses to TMT whether alcohol exposed or not-alcohol may change stress responses. With TMT there was a more sensitive interoception to alc.

Vecchiarelli, H. A. et al. Sex and stressor modality influence acute stress-induced dynamic changes in corticolimbic endocannabinoid levels in adult Sprague Dawley rats

Endocannabinoids activate CB1 which creates the effect of THC. Stress leads to less AEA (this activates CB1) which leads to more anxiety and the stress response. Male and female sprague dawley rats pair housed either went through a restraint stressor, a foot shock stressor, or a forced swim stressor. Researchers measured endocannabinoid ligand activity in the amygdala, hippocampus, and mPFC. EC responses changed depending on the type of stressor. Sex differences were minimal overall. Foot shock led to increased amygdala AEA and 2AG in hippocampus and mPFC. Restraint led to lower AEA in the mPFC. Swim stress led to lower AEA in the PFC, amygdala, and hippocampus. These may be neural feedback mechanisms for stress. Males may use EC to regulate stress more than females.

Temple, J. L. et al. Influence of caffeine on the liking of novel-flavored soda in adolescents.

Using human adolescents, researchers had them rank seven novel drinks. Their middle ranking was given to them six times over a week with either a placebo, 1mg, or 2mg/kg of caffeine. They also rated the bitterness, and other taste feelings. There was no change in the placebo or 1mg/kg group, however they did like their target beverage more at sixth visit. The 2mg/kg group had an initial decrease in liking then an increase over four days, and decreased perceived bitterness. 

Boggs, D. L. et al. The dose-dependent psychomotor effects of intravenous delta-9-tetrahydrocannabinol (Δ9-THC) in humans

CB1Rs are most prevalent in the basal ganglia and cerebellum. Looking at former acute cannabis users, abstained for three months, giving IV THC in a vehicle dose, low, or high dose, and looked at motor functions. Found a dose dependent deficit in fine motor control and motor timing. No change in gross motor or attention. Blood samples showed a similar level of intoxication across all doses (low, high) of IV THC.

Gutierrez, A. et al. Vapor exposure to Δ9-tetrahydrocannabinol (THC) slows locomotion of the Maine lobster

Restaurant workers wanted to see if there was a more humane way to kill lobsters. In rats, vaporized THC led to anti-nocioceptive (danger sensing behavior) and movement. Lobster neuromuscular junction may be regulated by cannabinoid receptors. They got one 6 second vapor puff every 5 mins over 30 or 60 mins. The 30 minute exposure condition had decreased locomotion. The duration of THC exposure had an effect on THC presence in muscle, brain, blood, clawtial muscle, heart, and liver. Only the 60 min exposure had a small effect on nociception behaviors (pulling claw away from hot water). Did find evidence that there is temperature dependent nociception in lobsters.

Chen, B. T. et al. Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking.

Deficits in the prefrontal cortex leads to impaired inhibitory control, which can lead to drug seeking even when there are consequences. Using male rats genetically altered to mimic cocaine seeking, there was an eight week training period for cocaine self administration on a chain schedule. Then, they went through four days of foot shock training where 30% of lever presses led to foot shocks. Researchers also optogenetically stimulated the PCF at the end of the baseline and end of the foot shock trials. Post mortem, electrophysiology was used to examine prelimbic cortex action potential activity.

Cocaine self administration led to pyramidal neurons in the prelimbic cortex to have less ability to make action potentials in response, more drug seeking in animals. Optogenetic stim of prelimbic cortex led to less drug seeking, optogenetic inhibition of prelimbic cortex led to more drug seeking

Terraneo, A. et al. Transcranial magnetic stimulation of dorsolateral prefrontal cortex reduces cocaine use:

To understand if TMS of the dorsolateral prefrontal cortex is safe and if it reduces cocaine use in humans, researchers split people with cocaine use disorder into control (pharmacological treatment) or repetitive TMS for 29 days. Then, they gave the option of everyone being able to undergo rTMS for 63 days. They found less cocaine use and cravings in the rTMS group in the first stage. Additionally, they found that those in the control group who moved to the TMS group had comparable benefits to the original TMS group