Neuroscience Flashcards
What is the name of the folds on the brain?
Gyrus (plural gyri)
What is the name of the fissures/grooves found on the brain?
sulcus (plural sulci)
Into how many areas did Brodmann classify the cerebral cortex
52
What is the somatosensory cortex?
major cortical areas receiving somatosensory information from the thalamus
What are the components of the basal ganglia?
– the caudate nucleus
– the putamen
– the nucleus accumbens
– globus pallidus
What is the function of the basal ganglia?
The basal ganglia can initiate motor activity and modulate indirectly the cortical output related to motor function.
It is also involved in non-motor functions including cognition, perception and emotional behaviours including the reward system.
What disorders is the limbic system often involved in?
Mood disorders
The limbic system is unique to mammals, true or false?
True
What is the function of the limbic system?
It is involved in modulation of hypothalamus function, hippocampus is involved in memory consolidation and formation, and the amygdala is involved in emotional response
What are some of the primary structures of the limbic system?
the amygdala, hippocampus, thalamus, hypothalamus, basal ganglia, and cingulate gyrus.
Why do we need the blood brain barrier?
CNS is and extremely sensitive system
and require, Maintenance of a highly controlled extracellular environment for neuronal function (e.g. ion concentration), and protection from potentially toxic chemicals derived from e.g. diet, infection, trauma
What is a neurovascular unit?
A collection of cells that make up the blood brain barrier
What do pericytes attached to the epithelial cell in the BBB likely do?
– Barrier permeability (e.g. via regulation of tight
junction proteins)
– Angiogenesis during development
– Clearance of tissue debris
– Neuroinflammation and leukocyte brain trafficking
What is the relation of solubility and molecular weight to diffusion across the BBB?
Diffusion across BBB is proportional to lipid solubility
and inversely proportional to molecular weight
Name two areas of the BBB, associated with reduced permeability.
– Arcuate nuclei
– Subfornical organ
What would be the effect of impaired leptin transport across the BBB on:
– NPY
– POMC
– Body weight
it would go up as leptin supresses these neurons
it would go down as leptin can’t stimulte it anymore
it would go up
What is the general function of leptin?
It is often referred to as the “satiety hormone” or the “starvation hormone.” Leptin’s primary target is in the brain, particularly an area called the hypothalamus and decreases appetite
What are three mechanisms of crossing the BBB
– Diffusion (primarily steroids)
– Penetration via ‘leaky’ regions of the barrier
– Specific transport mechanisms
What is kisspeptin involved in?
the regulation of reproduction
How long is the human kisspeptin initial hormone?
What are its cleaveage products?
145aa long
KP-54, KP-13 and KP-10
How long is the rat/mouse kisspeptin initial hormone?
What are its cleavage products?
130aa long
KP-52, KP-13 and KP-10
What receptor does kisspeptin act via?
GPR54 (KISS1R) receptor
What does loss of function of the GPR54 (KISS1R) receptor cause?
hypogonadotropic hypogonadism (underdeveloped gonads due to lack of gonadotropin hormones – LH and FSH)
How were people with a mutated GPR54 (KISS1R) receptor treated?
They were given GnRH (Gonadotropin-releasing hormone)
What gives evidence that KP acts through the GnRH receptor?
KP administration induces gonadotrophin secretion. GnRH receptor antagonists block this action
What type of receptor is GPR54/KISS1R?
A G-protein coupled receptor
Through what intracellular signalling pathway does kisspeptin activity occur?
Briefly describe this pathway.
phospholipase C
- KP activates PLC
- PLC hydrolyses PIP2 to generate the second messengers IP3 and DAG
- DAG activates protein kinases which in turn activate enzymatic pathways
- IP3 causes an increase calcium release thus increasing cytosolic calcium levels which activates enzymatic pathways
- PIP2 also causes rapid changes in ion concentration
In mice, where are KP neurones expressed?
the arcuate nuclei, periventricular nuclei and the anteroventral periventricular nuclei (all found in the hypothalamus)
Who showed that in mice reproductive physiology could be restored using KP?
Briefly describe their experiment.
León et al. (2016)
re-introduced expression of KP. The re-expressed animal organs were at an almost normal size compared to GPR54 KOs where they were greatly reduced. The same thing was found in male and female mice.
Which area of the brain is the rostral area?
Anterior or front
What would be the reproductive physiology of a Kiss1 KO mouse?
They would be reproductively inactive
What would be the likely reproductive effect of treatment with a GPR54 agonist in the following individuals?
– A 9 year old boy
– An infertile anorexic (30 years old)
In the boy it would likely stimulate development of reproductive system, however there are many factors that switch on puberty so KP might not be enough alone
In the anorexic you would expect the agonist to reactivate reproductive system
What is thought to be the role of leptin on Kiss1?
it is thought to be a permissive factor that may stimulate Kiss1 expression both in the AVPV and ARC (DeBond and Smith, 2014)
Name the three types of reproductive hormones and briefly describe them.
Gonadotrophin releasing hormone (GnRH).
More than 2000 found in the brain in the rostral area but also some are found caudally (in the ARC)
The gonadotrophins (LH and FSH). Glycoproteins that are involved in testosterone production and ovulation (LH) and spermatogenesis and folicular development (FSH).
Gonadal steroids, lipophilic hormones derived from cholesterol. Three main types: oestrogen, progesterone and testosterone
What age is the typical onset of pubertal development in boys and girls?
11 – 13 in boys
10 – 12 in girls
What does it mean by GnRH being both necessary and sufficient for puberty?
it must be there for puberty to occur
it is sufficient by itself to cause puberty to occur
In long-lived species what is the pattern of activation of the GnRH system?
Initial activation followed by a period of quiescence and then reactivation
puberty is reactivation of the GnRH system
In humans what causes elevated GnRH secretion?
an altered balance between GABAergic and glutaminergic input to GnRH neurones
other factors suspected to play a role: kisspeptin, glial cells, and nutritional/energetic regulation
Why is there a recent interest in appetite and energy balance research?
Global obesity rise: 1/3 in the UK are obese. Worldwide 39% overweight and 13% obese (WHO, 2014)
Obesity is a major risk factor for cardiometabolic diseases and some cancers. By improving understaning can make lifesyle changes and therapies
Name the key peripheral hormones that regulate appetite and describe how they interact with the brain.
Leptin: adipositiy marker, anorexigenic, acts on ARC and other parts of the brain, without it are obese
Insulin: secreted post parandially, circulating concentration proportional to adiposity, anorexigenic, acts on ARC , and elsewhere in the hypothalamus
GIT hormones:
- Ghrelin - orexigenic
- many examples of anorexigenic e.g. cholecyctokinin
What is stress?
a threat (actual or anticipated) to homeostasis
What is the autonomic response to stress?
reflex response to stress activates spinal preganglionic sympathetic neurones that target the cardiovascular system. Parasympathetic tone may also be modulated (and used to control sympathetic response)
What is the role of the paraventricular nuclei (PVN) in stress?
PVN is part of the hypothalamus important for integrating information from brainstem, and limbic system
contains CRH neurones and receives inputs that relate to physical and psychological stress
CRH and vasopressin then regulates other things
What is the role of pusatile hormone secretion in stress?
well described 24hr rhythm that peaks shortly before wake time
if sample more frequently find ultradian pulses
Walker et al. 2010 found increased frequency of pulses in chronic stress
How can stress modify CNS function on:
- behaviour and anatomy
- developmental programming
can affect cognition, mood and memory
found to affect remodelling of dendrites, neurogenesis and spine regulation
prenatal stress found to be linked to psychosocial problems observed in childhood and adulthood
What are the four stages of sleep?
N1: falling asleep
N2: sleep spindles and K complexes
N3: delta/slow wave sleep - deepest stage
R: rapid eye movement sleep
What are the 6 categories of sleep disorder?
- Insomnia
- Sleep related breathing disorders
- Central disorders of hyersomnolence
- Circadian rhythm sleep-wake disorders
- Parasomnias
- Sleep related movement disorders
What are some of the clinical symptoms of narcolepsy?
- cataplexy
- hypnagogic hallucinations
- sleep paralysis
- disturbed nocturnal sleep
Name three structural parts of the brain that are reduced in healthy ageing?
What remains unchanged?
Brain volume
Grey matter
White matter
Intracranial volume
Summary of the cellular hallmarks of the ageing brain:
What are the alterations of neuronal structure
NO substantial losss
Alterations to dendritic spines
Reduction of white matter
Alteration of synaptic function (reduced synaptic density, calcium homeostasis)
Microglial activation
What are the three methods by which animals can navigate?
Piloting - using familiar landmarks and visual clues over short distances
Compass orientation - using features of the earth’s environment such as magnetic filed or chemical cues
True navigation - cognitive map sense combined with a sense of internal timing that needs to be compensated for time
What is the name of the non-image forming light sensing organ in invertebrates?
ocelli
What type of neurotransmitter do most excitatory synapses in the brain use?
Glutamine
What are important receptors for LTP?
NMDA and AMPA
What is the brain region associated with Parkinson’s?
The substantia nigra
Where do GnRH neurons originate in early development?
The olfactory placode
