Unit 4 Flashcards
What is genetic sex?
- x/y chromosome complement
- x chromosome inactivation and escape
- sry gene
- epigenetics
Which partner determines sex?
fathers in humans
How many genes does the x chromosome have?
500
How many genes does the y chromosome have?
50 genes
What are the female chromosomes ?
XX
What are the male chromosomes ?
XY
What is gonadal sex?
- internal reproductive systems (testes and ovary formation)
- consequences of testicular testosterone surge and aromatization in early life, puberty and adult hormone cycles
What is gonadal sex directed by?
- early hormone exposure
What is the SRY?
- sex determining region
- encodes testes determination factor (TDF) on y-chromosome
What does the SRY do?
- causes embryonic undifferential tissue to develop into testes instead of ovary
What do embryonic testes secrete?
- testosterone and MIH
What can testosterone do?
- can bind to endocrine receptors or can be metabolized into estrogen
What is MIH?
- mullerian-inhibiting hormone
- causes regression of mullerian ducts
Are humans female by default?
- no, instead of SRY females have other inhibitory hormones maintaining the ovary
- there is active repression of transdifferentiating genes
Can gonadal sex and genetic sex be disassociated?
yes
What is phenotypic sex?
- external genitals
- secondary sex characteristics,
- behavior and neuron properties
What is gender identity?
individuals perception of their sex
What mediates the effects of biological sex?
- neural and gonads
- these influences can permanently sexually differentiate neurons or induce temporary, sex-specific changes
- environment can also change
Where do sex steroid hormones come from?
- synthesized from cholesterol
- can be produced by gonads under the direction of HPG- axis or locally synthesized neurosteroids in brain
- fatty structure allows for action at nuclear receptors or membrane receptors
- concentrations may vary based on brain region
What hormone is the most abundent in males?
testosterone
When do the testes release androgens?
- early development and adulthood
Are testosterone levels constant?
vary over the course of a day
How is T converted into estradiol?
- conversion happens in the brain by aromatase
When do ovaries release estrogen?
starting at puberty
What hormones are most prominent in females?
- estradiol and progesterone
Are estradiol and progesterone levels constant?
- no, vary based on cycle
- menstrual cycle is around 25 days
- estral cycle (rodents) is around 4 days
What can estradiol do?
- can act on multiple extranuclear receptor types to change neuron function
- effect depends on what receptor and where
- localization of receptors allows for a localized effect of steroid hormones
Is the neruoendocrine environment the same for all people?
no dynamic and varies by sex
What are the direct/ acute effects of sex steroid hormones?
- alter membrane excitability, sensitivity to NT, NT Release, especially in the presynaptic terminal
- modulate functions of enzymes, channels, NT receptors
What are the indirect/ long term effects of sex steroid hormones
- promote or inhibit gene transcription through action of cytoplasm
What is organizational hormone action?
- permanent, irreversible
- happens in specific developmental pyramids like early in life
- hormone binds, causes change, leaves, change stays
Where does organizational hormone action occur?
- brain and reproductive organ development
What is activational hormone action?
- temporary
- usually associated with adulthood, but can occur in any developmental pyramid
- hormone leave and change goes away
Where does activational hormone action occur?
- estrous and other mammalian sexual cycles
What happens if estradiol is metabolized?
it can be masculinized
What is the organizational / activational hypothesis posits?
- early hormone exposure organizes neural substrates subserving behaviors and later exposure activates the sexually differentiated the neural substances
Where is testosterone converted into estradiol by aromatase
cytoplasm
Do female gonads produce estrogen durin the early stages of deveopment?
no
What triggers the masculinization of the nervous system?
estradiol binding to estrogen
What can testosterone do?
- bind to androgen receptors to masculinize
- be converted to estradiol by aromatase
How can masculinization occur?
- through androgen receptors alone
- through estrogen receptors alone
- both
- which one is highly specified
- animal study: newborn female rats are treated with estrogen develop masculine behaviors and brain morpholgy as adults
What is neural sex differentiation dependant on?
- genetics
- epigenetics (environment)
- hormone exposure
- hard to generalize between neuron types
What are activational effects of basic hormone action?
- naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons
Where is the site of excitatory synapse formation on dendrites that have spines?
the dendritic spines
What happens in adult female rats with changes is estradiol and progesterone levels over the estrous cycle?
- the number of dendritic spines fluctuates
- increase in the hippocampal spine number coincides with female rat peak fertility
What are sex dimorphisms?
-clearly defined unconditional physical or behavioral differences between male and female individuals of the same species
What is an example of a sex dimorphism?
- lion’s mane or spinal nucleus of the bulbocaernosus (SNB)
What is the SNB?
- a neural sex dimorphism in rats
- SNB neurons innervate bulbovacernosus (BC) muscles at the base of the penis
- during early life more SNB neurons die in femaes than males
What is onuf’s nucleus?
- neural sex dimorphism in humans that is analogous to the SNB in rats
- located in sacral spinal cord
- innervate BC mucles surrounding the vagina and the base of the penis
- male is bigger because males have more motor neurons there
What are latent sex dimorphism mechanisms of E2-induced synaptic potentiation in the hippocampus?
- in females the presynaptic releases beta and post releases alpha
- in males the postsynaptic releases beta and the pre releases alpha
What is a latent sex dimorphism?
- one aspect of a trait is the same for females and males, but the mechanisms underlying the trait are different
- just the effect is the same
What is a sex difference?
- physical or behavioral difference between male and female individuals of the same species that vary along a continuum, data overlaps
What are examples of sex differences?
- height, differences in cognition
- ESPC frequency rat nucleus acumens core
- connectome
- dendritic spine density in hippocampal neuron
- a lot of unknown because not widely studied
- drug abuse
What are the sex differences in the connectome?
- males have greater ipsilateral connectivity and females have greater contralateral connectivity
- males and females differ in brain connectivity as a whole
- 100% of documented differences in neuroanatomy
What are some sex differences in drug abuse?
- higher rates of drug abuse in men, but sex differences in experiences and progression of addiction
- female rats acquire self- administration ore rapidly than males (willing to do a task for the drug more)
- discrete trial
- progressive ratio schedule
What is the discrete trial procedure for sex differences in drug abuse?
- rats have access to drug at certain periods of the day
- female rats exhibit extended binging and increased drug intake
What is the progressive ratio schedule for sex differences in drug abuse?
- progressive increase in responses required for drug infusion
- intact female rats reach higher final ratios than males
Where do sex differences occur?
- gentic, molecular, anatomical/physiological level
- occur in every organ measured so far
What two organs differ the most in terms of gene-expression between males and females?
- liver and brain
What is the problem with sex differences in trials?
- sex is widely undrported, we need more trials to record sex
- we need more trials to include both males and females (trials are going back to strictly male
What can sex differences at the neural level do?
- increase or decrease sex differences in observed behavior
What does the hypothalamus do?
-regulates all basic physiological needs
- maintains homeostasos
How does the hypothalalmus maintain homeostasis?
- gets info from internal sensors and nucleus of solitary tract (autonomic)
- compares info with set biological points
- integrates somatic behavioral info with autonomic visceral and endocrine responses
-makes adjustments where needed
How does the hypothalamus make adjustments to maintain homeostasis?
- behavior responses (somatic)
- ANS responses (visceral)
- endocrine responses (hormonal)
What are the parts of the hypothalamus?
- dorsal striatum
-NA - hypothalamic nucleus
- many more
What does the dorsal striatum control?
motor control
What does the NA control?
- reward and motivation
What does the hypothalamus control neuroendocrinally?
-feeding and reproduction
What is the hypothalamic nuclei?
- can be sexually dimorphic
-ex. SDN preoptic area controls male copopulatory info
How is the pituitary gland divided?
- anterior and posteriorly
What origin does the anterior pituitary have?
- non-neural origin
What origin does the posterior pituitary have?
neural origin
What are the two groups of neurosecretory neurons?
- magnocellular
- parvocellular
Where is the magnocellular gland?
-posterior pituitary
What does the posterior pituitary do?
- diancephalic structure
- releases neurohormones into circulatory system
What are examples of posterior pituitary hormones?
- oxytocin
- vasopressin
What does oxytocin control?
- uterine contraction
milk production
What does vasopressin control?
- blood volume and salinity by working with kidneys
What are neurohormones?
hormones released by a neuron
Where are the parvocellular glands?
- pituitary stalk
What do parvocellular glands do?
- releases hormones into portal circulation to act on cells in anterior pituitary, to make cells increase or decrease release
What are parvocellular homrone examples?
- gnrh
-somatostatin - anterior pituitary hormones like GH, LH, FSH
Is the anterior pituitary part of the CNS?
no
What is the parvocellular pathway?
- neural- non neural - effect
What is the HPG axis?
- example of parvocellular
- hypothalamus relesases GNRH into the antetrior pituitary which releases LH and FSH causing the gonads to release androgens and estrogens
- androgens and estrogens produced for both genders
- regulates gonadal hormone production in a negative feedback loop
What is the HPA axis?
- parvocellular
- paraventricular hypothalamus releases CFH into the anterior pituitary which releases ACTH leading to the adrenal cortex releasing cortisol
Is the HPA axis fast or slow?
- slow because it has to go through the bloodstream and the body needs to process what is happening
What does cortisol do?
- stress response
- mobilixes energy systems, supresses immune system
- cortisol crosses BBB
How do diffuse modulatory system work?
- metabotropic receptors
How are diffuse modulatory systems named?
after the primary NT used
What are diffuse modulatory systems made of?
- large number of neurons
- small number of cell bodies ( around 1000) in 1 or a few nuclei
- typically in or around the brainstem
-axon connections are formed by individual neurons, a single neuron can innervate different targets
What is the dopamine system?
-controls motivation and reqard
- goes from SNPC to dorsal striatum and other places
What does the ventral tegmental area do?
- sends dopamine to ventral striatum and NA
What is motivation?
- change in behavioral response to a consistent stimulus due to a change in endogenous state
- encompassses feeding, sex, affilative behavior, drug seeking
What is the appetitive stage of motivation ?
- anticipatory stage of motivation
-search phase - more variable and spontaneous
What is the consumatory stage of motivation?
- sterotypic phase that results in termination of behavior sequence
How is domapine measured?
- using electrochemical or micro dialysis techniques
Where does the NA get inputs from?
- PFC, HC, BLA, CTA, VP
Where does the NA send input to?
- VTA and VP
What part of the NA get D1 and D2?
- the core and the shell
How can you increase a DA response?
- put an electrode in the mesolimbic projection because it is more direct and doesn’t have the same inhibitory synapses the VTA could have, nd other effects NA could have
- also gets DA where it needs to go
What does serotonin control?
- emotion
- heavily innervates the limbic system
- general arousal
-sleep-wake - mood (especially aggression)
- emotional expression (physiology)
- emotional experience (feeling and cognitive)
Where is serotonin produced?
- dorsal ralphe
What does the limbic system include?
- prefrontal cortex, cingulate gyrus/cortex, anygdala, parahippocampal gyrus, basal ganglia, NA
What is the NE system?
- in charge of general arousal, sleep wake cycle, attentiveness
Where does NE come from?
- locus correolus and other brainstem nuclei
What is the ACH system?
- in charge of sleep-wake and learning and memory
- part of basal forebrain complex
What does cocaine do to the mesolimbic system?
- blocks DA reuptake by Da transporter on NAC
- BLOCKS
- side effect is less sleep
What does amphetamine do to the mesolimbic system?
- reverses DA transporter in NAc so DA comes out
- REVERSES
- side effect: less sleep
What does PCP do to the mesolimbic system?
- blocks glutamate receptors in NAc including projections from the amydgala
- associated with a lack of fear
What does nicotine do to the mesolimbic system?
- acts on ACHRs present of NA presynaptic terminals
What do opiates like heroin do to the mesolimbic system?
-inhibit neurons that release GABA onto VTA neurons
What does alcohol do to the mesolimbic system?
- complex effects
- includes inhibition of GABAergic neurons
What does ecstasy (NMDA) do to the mesolimbic system?
- may block DA reuptake and inhibit GABAergic neurons
- cold be used to help fear disorders like PTSD
What do cannabinoids do to the mesolimbic system?
- increase excitatory input into VTA
What do addictive drugs do to the mesolimbic system?
- individual effects are different from acute effects
- affects addictive pheontyps and liabilities
- there is s spectrum of addiction likelyhood
- all drugs hijack a part of the mesolimbic system
What is learning?
- acquisition of new knowledge/skill
What is memory?
- retention of learned knowledge
- short and long term and working
What is short-term memory?
- temporary like seconds or minutes
What is long-term memory?
- held in brain for days weeks or years
What is working memory?
- what we keep in mind but lose if distracted
What are the phases of learning?
- encoding
- consolidation
- storage
- retrieval
What is encoding?
-info first gets into brain and processed
What is consolidation?
- info moved into storage
- takes time
What is storage?
- builidng and strengthening of networks of neurons to store info
What is retrieval?
- access to info when needed
What is the story of HM?
- severe epilepsy led to bilateral temporal lobe resection
- lost short-term memory, kept some long-term
- still had sequential memory
- he couldn’t remember anything but could still learn
- his hippocampus lost the ability to consolidate info
- still had good working memory
What is explicit memory?
- facts, events,
- requires deliberate consciouss effort
What is non-declarative/implicit memory?
- procedural memory
- classical conditioning
- no conscious awareness
- more reflexive than reflective
What is procedural memory?
- skills and habits
What are the types of classical conditioning?
- motor
- perceptual
- emotion
What is retrograde amnesia?
- a loss of memory- access to events that occured or info that was learned before an injury or disease onset
What is Anterograde amnesia?
-loss of ability to create new memories after an event leading to a partial or incomplete ability to remember new events and recent past.
- still have long term memory
How can you test declaritive memory?
- how many numbers can you remember
- delayed match: put out three objects, switch objects, try and remember which ones were og
What does the chemical structure of a drug determine?
- binding
- location
- affinity
- strength
Does the timing and type of drug administration matter?
yes it determines the strength of drug
What are the basic categories of neuropeptides?
- amino acids (small organic molecules)
- amines (small organic molecules)
- peptides (proteins)
What is a drug?
- any substance your body doesn’t produce that binds to the receptors in your body
What does a drug do?
- depends on the receptors they can bind to
- mimic or block the actions of our endogenous NT
Are natural drugs safer than man made ones?
no it depends on the actions on the body
What is binding affinity?
- the degree of chemical attraction between a ligand and a receptor
What is efficacy?
- the ability of a bound ligand to activate the receptor
What are competitive ligands?
-drugs that bind to the same receptor site as the NT
What is a noncompetitive ligand?
- binds instead to a modulatory site on the receptor
Are competitive or noncompetitive ligands agonists or antagonists?
- could be either
What is a dose-response curve?
- a graph of the relationship between drug doses and the effects
What are pharmacodynamics?
the relationship between drugs and their targets
What is potency?
- the amount of drug needed to produce and effect
What is efficacy?
- the amount of response a drug has at a specific dose
What is a metabolic tolerance?
- organ systems become more effective at eliminating the drug
What is functional tolerance?
- target tissue may show altered sensitivity to the drug
What can cause tolerance?
- changes in numbers of receptors can alter sensitivity in a direction opposite to the drugs effects
- down regulate or up-regulate
What is down regulation?
-turn down the number of receptors that can bind
- more common than upregulating
Why is upregulating uncommon?
- energy consuming
- not needed as often
What is cross-tolerance?
- tolerance to a whole class of chemically similar drugs
What is sensitization?
-drug effects become stronger with repeated treatment
What happens when there is too much glutamate or excitation?
-seizures and convulsions
What point in the synaptic transmission process do drugs affect?
- can affect literally all points pre-synaptic or post-synaptic
What type of drug administration is the fastest?
- IV is fastest. inhalation is a very quick second best
What type of drug administration is the slowest
transdermal diffusion
What type of drug is used for schizophrenia?
- d2 receptor antagonists
- sometimes serotonin receptors
What type of drug is used to treat anxiety?
- GABA receptors
What type of drug is used to treat depression?
- monoamine NT increasing
- MAOI
-tricyclics - SSRIs
What does alcohol affect?
-gaba receptors
- biphasic - initial stimulant followed by prolonged depression
- lowering of inhibitions
What is the main ingredient in cannabanoids?
delta 9 thc
What are the cannabanoid receptors?
cb1 cb2
What are nicotine receptors?
- ACH
What does cocaine do?
- locks reuptake of monoamine transporters
What is a dissociateive drug?
- produces feelings of depersonalization and detachment from reality
What is the dissociative drug receptors?
- antagonists to nmda receptors
What are examples of dissociative drugs?
-pcp ketamine
Where is memory of faces stored?
- vetral visual stream
- temporal cortex
What does more neurons mean in terms of memory?
more neurons= stronger memory
What is the halle berry experiment?
- showed faces of celebs and saw if people could recognize them
- measured medial temporal cortex and amount of AP firing with each face
- measured medial temporal cortex and amount of AP firing with each face
- used to find the pathway for face recognition
How does face recognition and memory work?
- strengthening requires synaptic plasticity
- LTP is for declarative memory
- must be activity on both sides of the synapse
- what wires together fires together
What can some forms of NMDA antagonists do?
- block declaritive memory because it has to do with hippocampus
What does short term memory have to do with LTP?
- if something can be forgotten there is a back and forth or on and off of LTP
-LTP and LTD - more Ca2+ correlates to more LTD which can be seen with shorter more powerful stimmuli
What can affect long term memory?
- genetics
- gene expression
- neurons
- dendrite structure changes
What is the most common type of memory loss?
- alzheimers
What is dementia?
- a loss of cognitive funciton
What is alzheimeres caused by?
- amyloid plaque build up
- can see senile plaques from estracellular deposits of amygdaloid
- tau tangles
- disease of the synapse?
What is the least affected lobe when it comes to alzheimers?
- occipital lobe and broadmans area 17
