Behavioural Neuroscience Studies

• Discovered the intense electrical stimulation of axons leading from the entorhinal cortex to the dentate gyrus caused a long-term increase in the magnitude of excitatory postsynaptic potentials in the postsynaptic neurons (LTP)

• Strenghtening of an individual synapse is accomplished by insertion of additional AMPA receptors into the postsynaptic membrane of the dendritic spine.

• Found that lesions of the SCN decreases masculine sexual behaviour.

• Persistent Mullerian duct syndrome has two causes: either a failure to produce anti-Mullerian hormone or the absence of receptors for this hormone.

• Male rats born to stressed mothers are less likely to display male sexual behaviour.

• In rats, being next to a male fetus increases female blood levels of testosterone.
• 2M females are more likey to engage in inter-female aggressiveness.

• Control of aggressive behaviour in adult female rats.
• Estradiol = no effect on frequency of fighting
• Testosterone = increases frequency of inter-female aggression
• Activational effect required

• Reduction in testosterone levels leads to reduction in sexual behaviour.

• Thinking about sex increases levels of testosterone.

• Fluctuations in ovarian hormones showed little correlation with sexual activity.

• Women attending an all female college had synchronized menstrual cycles.
• Pheremones

• Males reported sweaty t-shirts from a female in their fertile phase as more pleasant.

• Study on 30 women with CAH reported incidence of homesexuality 4 times higher than in wider population.

• Cases of androgen insensitivity show no indication of sexual interest in women.

• Maternal stress in rats leads to reduced exposure to androgens, reduced sexual behaviour in males and a reduced preoptic area of the hypothalamus.

• Females and male-to-female transexuals have a smaller bed nucleus of the stria terminalis than males.
• No difference between hetero and homosexual males.
• Size related to gender identity, not to sexual orientation.

• Prolactin stimulates next building in females.

• In rats, lesions of the MPA leads to them not caring for the pups.

• Increased levels of oxytocin facilitated maternal behaviour.

• An fMRI study found that when mothers looked at pictures of their infants, brain regions involved in reinforecement and those that contain receptors for oxytocin showed increased activity.

• No sexual dimorphism in MPA of prairie voles.
• Monogamous

• Found that fathers with higher blood levels of prolactin reported stronger feelings of sympathy and activation when they heard cries of infants.

• Studied pairs of male twins - concordance rate 52% for identical twins and 22% for fraternal twins regarding homosexuality.

• Found that neurons of the MPA that are activated by the performance of maternal behabiour send their axons to the ventral tegmental area (VTA). Cutting the connections of the MPA with the brain stem abolishes maternal behaviour.

• Measured adenosine levels - increased during wakefulness.

• Mice with mutation to reduce production of adenosine had less slow wave sleep.

• WW1 victims of encephalitis lethargica caused some to sleep continuously and others to sleep little.
• Damage to posterior hypothalamus and adjacent midbrain leads to excessive sleep.
• Damage in anterior hypothalamus or preoptic area and adjacent forebrain leads to wakefulness.

• Used microdialysis probes to measure the release of ACh in the hippocampus and neocortex.
• Found levels of ACh in these regions were high during waking and REM sleep but low during slow-wave sleep.

• Rats born and raised in unchanging light environment showed 25 hour cycles.

• Humans have innate sleep wake cycles of 25.3 hours.

• Lesions of the suprachiasmatic nuclei abolishes sleep patterns.

• Control hamsters: 25 hour clock
• Mutant hamsters: 20 hour clock
• Transplanted hypothalamus of mutant into control and vice versa - they switched cycles.

• Adaptive theory
• No function of sleep other than to keep out of harms way when nothing important to do.

• Randy Gardiner's world record - 200 hours awake
• Following sleep deprivation, participants do not catch up on all their missing hours of sleeo
• However, following sleep deprivation only 7% of stages 1 and 2 were made up compared to 68% of stage 4 SWS and 53% REM sleep were made up.

• Sleep deprivation does not disrupt ability to do complex cognitive tasks.

• Indus dolphins - River Ganges - have to stay awake - microsleep

• Animal studies into sleep deprivation had fatal consequences.
• Rats on rotating platform - experimental chamber - REM sleep = platform moves.
• After 4/5 days the experimental rat died.

• Stimulated a person's hand, more delta activity was recorded in the contralateral somatosensory cortex during sleep - rest/restore

• Rats in warm chamber exhibit more slow wave activity.

• Subjects learned declarative learning task and a non-declarative learning task.
• After a nap, including SWS, only subjects who learned declarative learning task showed improvement versus those who stayed awake.

• Trained people on virtual town - had to learn a route.
• fMRI showed activity in the hippocampus during route learning, activity also shown in this area during SWS but not REM sleep.

• Trained people on virtual town - had to learn a route.
• fMRI showed activity in the hippocampus during route learning, activity also shown in this area during SWS but not REM sleep.

• Trained people on virtual town - had to learn a route.
• fMRI showed activity in the hippocampus during route learning, activity also shown in this area during SWS but not REM sleep.

• When Ps awakened in slow wave sleep, those that reported thoughts relating to the task were subsequently much better at the task than those that reported thoughts not related to the task.
• Suggests consolidation occurs during SWS.

• REM sleep deprived rats learn tasks more slowly than control rats.

• Showed biggest increase in rate of learning follows large increase in REM sleep.

• Found students' REM sleep increases during exam period.

• 90 minute nap including SWS and REM - improvement seen on nondeclarative task.

• After several days of sleep deprivation, subjects would show a rebound phenomenon - greater than normal % of the recovery night spent in REM sleep.
• Suggests there is a need for a certain amount of REM sleep.

• Increased activity of amygdala in convicted murderers - particularly murders associated with emotion.

• Risk taking in monkeys related to low levels of serotonin

• Reduced levels of serotonin to ventromedial prefrontal cortex seen in impulsive aggressive individuals.

• found that fluoxetine (Prozac) a serotonin agonist decreased irritability and aggresiveness

• Showed the VmPf cortex bcame active when making emotional decisions.

• Patients with Urbach-Wiethe disease which damages the amygdala have difficulty recognisng fear.

• Facial expressions similar in blind and sighted children

• Series of photographs
• People in isolated tribe in New Guinea easily able to say what emotion was

• Japanese v. American culture
• Group of teenagers - horror film - when alone showed same reactions
• When with lab assistant - Japanese more subdued

• Showed removal of amygdala meant rats did not show CR to a tone that predicts a shock

• Microexpressions

• Chimera photos
• Express emotions with half of face
• Spreads from left to right

• Ps that were instructed to smile rated pictures more positively, and those instructed to frown rated them negatively.

• Contractions of facial muscles on left led to negative emotions.
• Contractions of right muscles led to positive emotions.

• more EEG activity in left frontal cortex when smiling
• more activity in right when frowning

• Damage to right somatosensory cortex disrupts ability to recognise emotionas.
• Less likely to copy others emotions, can't understand how they are feeling

• Patients with damage to spinal cord rate emotional pictures.
• More emotion if damage was lower down, more repsonse from body.

• found that interfering with muscular movement associated witha particular emotion decreased the participant's ability to experience that emotion

• found that patients with right hemisphere damage had difficulty producing or describing mental images of facial expressions of emotions

• damage to left side improves ability to spot a liar - focus more emotion not understand meaning of words

• PET scans show activity in amygdala when shown faces expressing fear

• Damage to insular cortex and basal ganglia impairs ability to recognise disgust

• Innate preferences for sweet and salty things.
• Aversion to bitter tastes.

• Blood glucose levels reduces between meals.

• Receptors in the liver can stimulate glucoprivic hunger - neurons deprived of glucose stimulate eating

• blood glucose levels do not normally vary even under prolonged period of fasting

• Blood leves of ghrelin increase shortly before each meal, which suggests that this peptide is involved in the initiation of a meal.

• Found a single injection of ghrelin not only enhanced appetite, it also elicited vivid images of foods that the subject liked to eat.

• Paired buzzer with food, and bell with inter-meal times
• Pressed lever for food when they heard buzzer but not bell

• OB mice
• Obese strain
• Don't produce leptin
• When leptin injected, lose weight
• Meal size reduced

• Inflated bag in stomach, when stomach empty they felt bloated, when fats infused into duodenum they felt full

• Students swallowed rubber tube pumped with food
• When they tasted the food - ate more

• removed nutrient content and replaced it with water
• rats continued to eat until nutrients restored

• Peptide YY released by stomach after meal in proportion to calories consumed

• not adaptive to have a set point - need to store food

• Trying new pestkillers - also killed birds of prey
• Smaller birds gained weight as threat was reduced

• Pima Indians - those who moved to America increased in weight compared to those who stayed in Mexico

• showed that rats that were stressed ate more

• Twins had high concordance rate for weight gain and in the same place

• Twins had high concordance rate for weight gain and in the same place

• although high blood levels of leptin in obese people, it wasn't transferring to cerebrospinal fluid and therefore not to brain centres

• fed people a diet for 8 weeks that contained 1000 calories more than usual
• 39% converted into fat tissue
• 26% increased resting metabolic rate
• 33% increase in NEAT (non exercise activity thermogenesis)
• Amount of fat tissue a person gained was inversely related to their level of NEAT

• Increasing levels of uncoupling protein (UCP) associated with increasing metabolic rate and so less glucose left over to sotre as fat

79 panic disorder patient probands - interviewed 220 first degree relatives - 9% risk

first degree relatives provide acquaintance list of non-ill - interviews with 231 first degree relatives - 3% risk

Little Albert

White rats and hammer

Generelisation

Critics

tPA increases excitotoxicity, futher damaging the brain

tPA increases excitotoxicity, futher damaging the brain

tPA increases excitoxicity, further damaging the brain

tPA increases excitoxicity, further damaging the brain

Research with laboratory animals indicates that desmoteplase causes no excitotoxic injury when injected directly into the brain.

A clinical trial of desmoteplase found that it restored blood flow and reduced clinical symptoms in a majority of patients if given up to 9 hours after the occurence of a stroke.

Enrolled chronic stroke patients in a course of therapy that combined repetitve practise of hand and arm movements used in every day life and watched videos of actos doing the same v. videos of sequences of geometric shapes.

Patients' motor functions showed long-term improvement relative to geometric shape group.

Mirror neurons in parietal lobe and ventral premotor cortex became active when person performs an action or sees someone else perform it

Brains of people with several other degenerative diseases - including Alzheimer's disease - also contain aggregations of misfolded proteins

Normally proteasomes will destroy the misfolded proteins. Parkin, a gene on chromosome 6 plays a role labeling and ferrying the misfolded proteins to the proteasomes.

The main difference between nigrostriatal system and mesolimbic regarding dopamine = calcium channels are involved in regulating the spontaneous activity of DA cells in the nigrotriatal system and soduim channels are involved in activity of those in mesolimbic system

DBS of the subthalamic nucleus is as effective as brain lesions in suppressing tremors and has fewer adverse side effects.

Destruction or removal of the Globus Pallidus which inhibits the motor cortex has been found to alleviate symptoms of Parkinsons

Introduced a genetically modified virus into the subthalamic nucleus of patients with Parkinson's disease that delivered a gene for the enzyme (GAD) which prodcues the inhibitory neurotransmitter, GABA.

Decreased activity of the GP - and thus increased the activity of the motor area cortex and the symptoms improved

Performed scans on patients with high risk of AD and found evidence of reduced brain volume, particularly in parietal lobe, up to 5 years  prior to AD diagnosis

found that in brains of mild AD patients there was a 32% loss of neurones in entorhinal cortex - connected to hippocampus

In AD, spatial disorientation often first symptom seen by family

Showed patients with early stage AD also made more mistakes on a newly learned route, particularly when asked to travel route in reverse, but not impaired on tests of memory

Tested patients on their ability to recall a route through a hospital, patients with AD became lost more than age matched controls and had more difficulty recognising landmarks on route

Abnormal APP genes cause the defective long form of AB(beta) to be produced

attempted to sensitize the immune system against AB(beta) - injected AD mice with a vaccine that they hoped would stimulate the immune system to destroy AB - the treatment worked - suppressed development of amyloid plaques in brains of mice that received the vaccine from an early age

Meta analysis

prevalance of szhizophrenia

LIfe Time Prevalence = 1-1/1000, 0.4% on average

Schizoprenia inheritance:

2 parents with S - only 34% chance of being schizophrenic

schizoid + schizophrenic = 66%

multiple genes? predisposition?

Schizoprenia inheritance:

2 parents with S - only 34% chance of being schizophrenic

schizoid + schizophrenic = 66%

multiple genes? predisposition?

more direct evidence for link between influenza and schizophrenia

64 cases of schizophrenia spectrum disorders - mothers had give blood samples during pregancy

SSD - 21% exposed to infection of influenza in first half of pregnancy v. 9% controls

role of cannabis in schizophrenia

750ps, longitudial

pos correlarion - those who smoke cannabis at 15, more likely to experience psychotic symptoms and illness by age 26

no link to depression etc.

Support for dopamine hypothesis

S patients showed a more marked dopamine response to amphetamine, a DA agonist, than controls

in addition there was a correlation between the repsonse and the change in subjectively experienced s symptoms

mRI scans of schizophrenics and controls during cog. task

in inctrols, dorsal lateral prefrontal cortex highly active

gone in S patients

mRI scans of schizophrenics and controls during cog. task

in inctrols, dorsal lateral prefrontal cortex highly active

gone in S patients

unipolar and bipolar disorder

MZ - 40% BPD vs. DZ - 5.4% BPD

MZ - 44% UPD vs. DZ - 20% UPD

genetic contributions

Rats given inescapable shocks or nothing - shuttlebox - move from one side to the other, could escape by changing sides when light came on

Control - only failed to escape on 4 occasions

Shocked - various doses of fluoxetine (Prozac - SSRI)

0 = failed on half

7.5 = failed to escape most

15 = learned helpessness effects reversed

30 =

did process of tryptophan low/normal diet and amino acid drink with patients in remisson from depression and saw immediate relapse and recovery as normal diet was reinstated

Positive correlation between childhood maltreatment and adult depression but the effect of stress was moderated by presence of short-alleles for the 5-HT transporter gene

High 5-HT during development is associated with increased risk of adult depression - short = ess effective re-uptake

seasonality effect

studied month of birth of over 13,000 schizophrenic patients born in scotland

found dispropotionately more patients born Feb-May

Notes the winter flu season coincides with the second trimester of pregnancy of babies boring in late winter and early spring

studies effects of maternal use of tobaco, cannabis or alcohol and found that tobacco use during pregnancy was associated with increased risk

found that close relatives of people who suffer from affective psychosis are 10 tims more likely to develop these disorders than are people without affected relatives

found DBS of the nucleus accumbens did reduce the symptoms of depresion in 50% of treatment-resistant patients who hdd previously shown no responses to phatmacological treatment or ECT

Between 70 and 80 percent of patients with bipolar disorder show a positive response to lithium within a week or two.

preparedness theory, selecive associations

both groups of rats drank bright noisy and tasty water

one group given lithium chloride - nausea

other given electric shock

gustatory and tactile US

tasty water intake reduced in lithium chloride group

bright noisy water intake reduced in immediate shock group

predisposed to learn particular associations

ps viewed series of slides for 8s each

phobic stimuli and neutral stimuli

half subjects, phobic group, snake pics followed by shock but other half, neutral pics followed by shock

skin conductance

half then instructed there would be no  more shocks and other half left to find out

phibic stimulus - still responded strongly when told

neutral - weaker responses

198 Ps - anxiety disorders

carbon dioxide challenge - 5.5% enriched air - feel breathless

panic disorder Ps showed higher levels of panic symptoms after - shws rarly symptoms may act as a cue for later

blue or yellow colour as CS

electric shock 1/2 and 1/2

skin conductance

acquistion and extinction procedures employed and fMRI scans used to examine amygdala responses during each phase

activated stongly during acquisition phase vs. extinction phase

Brain derived neurotrophic factor (BDNF) and fear conditioning

Plays a role in neurogenesis - takes place in the hippocampus of the developed brain - important in learning - BDNF mutations show deficits in extinction of CRs to aversive CSs

found that rats could be trained in an operant task to lever press in order to obtain stumulation of the septal region of the forebrain

found conditioned place preference - applied EBS in particular corner - animal came back quickly

Smokers attended 6 sessions each fo 6 hours

Placebo  , 1mg or 2mg of haloperidol - a potent dopamine antagonist

Waited 3 hour period then allowed to smoke ad-libitum - subjects smoked either nicotinised or de-nicotonised cigarettes in each session smoking reduced

Suggests dopamine is also involved with secondary reinforcement

Smokers attended 6 sessions each fo 6 hours

Placebo  , 1mg or 2mg of haloperidol - a potent dopamine antagonist

Waited 3 hour period then allowed to smoke ad-libitum - subjects smoked either nicotinised or de-nicotonised cigarettes in each session smoking reduced

Suggests dopamine is also involved with secondary reinforcement

Classical and operant conditioning in addiction

used a second order schedule to study separately the contribution of cc and the role of drug infusions

nicotine infusions on every 10th response and light

then substitutte saline - responding reduced

then mecamylamine - nicotine anatagonist - reduced further

light omitted - response reduce, fall apart

alcohol preferring rats showed enhanced startle responses and the response was reduced by ethanol

reduce impact of stressors

negative reinforcement