Belovich- Brain and Behavior: Molecular basis of cognition Flashcards
Where is information integrated in a neuron?
cell body
Output signal is the chemical release of?
neurotransmitter
Neurons are classified by output/input?
output
What are the main 2 AA types of neurotransmitters?
- Glutamate
- GABA
What is the main action of glutamate as a neurotransmitter?
excitatory
What is the main action of GABA (neurotransmitter)?
globally inhibitory
What are the 4 main monoamine neurotransmitters?
- Dopamine
- Serotonin (5-HT)
- Norepineprhine
- Histamine
What are the 5 main types of neurotransmitters?
• Amino Acids
• Glutamate • GABA
• Monoamines
• Dopamine • Serotonin (5-HT) • Norepineprhine • Histamine
• Acetylcholine
• Nitric Oxide (gas, diffuses across cell membrane)
• Peptides (enkephalins, endorphins)
The majority of neurons signal using acid neurotransmitters
glutamate and GABA
amino
What are the two main neurotransmitter receptors?
What neurotransmitter receptor is the fastest?
• Ionotropic receptors
• A.K.A ion channels • Rapid intracellular changes (msec - sec)
Which neurotransmitter receptor is the main target for pharmacological drugs?
• G-protein coupled receptors (GPCRs)
• A.K.A. metabotropic receptors • Effects can last tens of seconds to minutes
Monoamine receptor agonists and antagonists have both and central effects
peripheral
Which type of neurotransmitter receptors Contribute to therapeutic, ontarget, and off-target effects of psychotropic drugs?
Monoamine
Where are muscarinic receptors expressed?
ANS and CNS
alpha and beta receptors are expressed peripherally and .
Centrallly
Which monamine neurotransmitter is being described?
Histamine
Which receptor subtype for Histamine leads to decreased AC and which results in the antagonist to treat sleep disorders, obesity, and dementia
H3
Which monoamine neurotransmitter is described?
norepinephrine
What is the result of norepi acting as an agonist and interacting with a2A,B, and C neurotransmitter receptors?
sedative and hypertensive, inhib AC
What is the proprosed clinical significance of the effect of norepi on the B1 receptor?
Regulation of cardiac function, antagonists may be anxiolytic
What transmitter type is described below?
seratonin
What drug in a partial agonist of the 5HT1 receptor and acts as an axiolytic and may have a role in hippocampal neurogenesis
Buspirone (serotonergic)
5HT2 receptors deal with which transmitter?
seratonin
What effect do 5HT2A antagonsist have?
antipsychotic effects,
What clinical effect do 5HT2A agonists have?
hallucinogens;
What 2 main receptors receive dopamine and what are the clinical effects?
D1 agonists are used to treat which dz?
Parkinsons
D2 antagonsists have what clinical significance?
Antiphsycotic (haloperidol)
D3 agonists treat which 2 diseases?
used in Parkinson’s disease, restless legs syndrome (e.g., pramipexole)
What type of receptors reside on the cell body or terminal of the presynaptic neuron and Activation results in reduced release and/ or synthesis of neurotransmitter?
autoreceptors
Which two autoreceptors have clinical significance?
Serotonin and dopamine autoreceptors have clinical significan
What part of a neuron works as a detector of the amount of neurotransmitter in the synapse?
autoreceptor
Which 5-HT receptor, if manipulated, is associated with anxiety?
5-HT1a
Which 5-HT receptor, if manipulated, is associated with migraines?
5-HT1d
Activation of autoreceptors results in increased/reduced release and/ or synthesis of neurotransmitter?
reduced
Neuropeptides act as transmitters, hormones, or
modulators
Axonal transport is required for to reach synaptic bouton from nucleus
neuropeptides
Why is Axonal transport required for neuropeptides to reach synaptic bouton from nucleus?
they are synthesized near the cell nucleus
Neuropeptides do/do not always evoke an action potential
do not
In what ways can neuropeptides modulcate the effects of neurotransmitters?
enhance or diminish
What are the differences between AA neurotransmitters and neuropeptides?
AA neurotransmitters are synthesized near buton
Neruopeptides are synthesized near cell nucleus, deliver long term signalling= more chronic effects
and hormones play an important role in psychiatric conditions and mental health
Neuropeptides
What hormone stimulates release of cortisol?
Adrenocorticotropic hormone (ACTH)
What hormone is released as a response to physical, mental and emotional stresses (esp. chronic)?
cortisol
Hormone levels (growth, thyroid, cortisol, etc.) can/cannot be altered in patients with psychiatric symptoms
can be
What is the focus of growth hormone in children vs adults?
child- height
adult- muscle density
Adrenocorticotropic hormone (ACTH)
Angiotensin
Dynorphin
ß-Endorphin
Enkephalins
Growth hormone
Neuropeptide Y
Orexin
Substance P
are all examples of what?
neuropeptides
Studying Monozygotic vs. Dizygotic twins • Controls for shared environment
in utero
Twins Raised apart vs. raised together • Controls for factors (parenting style, diet, etc.)
environmental
Personality traits are, on average, more strongly correlated with than environment.
genetics
Monozygotic twins raised apart still show behavioral similarities. T or F
True
Some psychiatric conditions are linked to a chromosome
• Most behaviors are composed of complex genetic and (likely) interactions
epigenetic
Behaviors rarely/often affected by a single mutation.
rarely
psychiatric illness Symptomatic individuals usually have disruptions in gene networks or functions including:
Cell-to-cell signaling, neuronal differentiation, neuronal migration, organization of cortex, etc.
Genetic risk factors can lend susceptibility to developing phenotypes based on and
environment, experience
can host mutations, but are not exposed to environmental triggers
Carriers
Early experiences and developmental environment can/cannot influence the effects of genetic factors
can
What is the effect threshold as concerning pathopsychiatric symptoms?
pass the threshold = loss of function = symptoms
Neural development is influenced by both and environment
genetics
The developing brain is susceptible to environmental and cues- the number of synapses and where they grow from
epigenetic
Epigenetics can/cannot be carried over to the next generation
can
Purkinje neuron cells are specific to the
cerebellum
Pyramidal cells are associated with the
hippocampus
What 6 main characteristics and mechanisms are involved with the development and growth of individual neurons?
- Genetic identity of the cell type (determines what cell looks like)
- Neuronal migration to appropriate cortical region
• Neuronal Growth Factors that determine cell survival
• Functional activity from other neurons = “Neurons that fire together wire together”
• Dendritic arborization and
synaptic pruning
Neuronal migration to cortical layers is encoded
genetically
Neurons use cells as migratory scaffolds
radial glial
How many neuronal layers in the mature cerebral cortex?
6
Evidence of patches of disrupted cortical layers in post-mortem patients with Disorder
Autism Spectrum
What two glial cells support and insulate neuronal axons in the CNS and PNS?
Oligodendrocytes and Schwann cells
Astrocytes support neurons in four ways:
- Insulating groups and synaptic connections
- Regulation of K+ concentration in the space between neurons
- Reuptake of neurotransmitters from synaptic zones after release
- Release of growth factors to surrounding neurons
Which hypothesis is being described below?
While growing, neurons extend axons to target cells that secrete low levels of neurotrophic factors (NTFs) =transported back to the neuronal cell body to indicate everything is good
Neurons in proximity to a source of NTFs survive and may grow new synapses
- Neurons that fail to receive adequate amounts of neurotrophic factor undergo apoptosis
- Astrocytes release neurotrophic factors to support neuronal survival
Neurotrophic Factor Hypothesis and Development
What are neurotrophins?
growth factors
What are the 3 major neurotrophins?
Nerve Growth Factor (NGF)
- Brain-derived neurotrophic factor (BDNF)
- Neurotrophin-3 (NT-3)
Neurotrophins interact with what kind of transmembrane receptor?
tyrosine kinase receptor (Trk receptors)
Neurotrophin binding induces and phosphorylation of Trk receptors
dimerization
Identity of the protein mediates either neuronal differentiation (pyramidal or purkinje) or survival
adaptor
promote neuronal survival by inhibiting apoptosis
Neurotrophins
What are the extrinsic death signals that can trigger neuronal death ?
Extrinsic death signals: tumor-necrosis factor (TNF)
Which of the major 3 neutrophins is associated with depression?
Brain-derived neurotrophic factor (BDNF)
What are some intrinsic factors that could trigger neuronal cell death?
stress induced signals; DNA damage
What proteins are activated when extrinsic or intrinsic factors signal neuronal cell death?
caspases -cleaves DNA = cell death
Activation of receptors, activated by neutrophins, inhibits caspase pathway via PI3 kinase/Akt signaling
Trk
What is the result of insufficient neurotrophins in developing neurons?
leads to apoptosis
What cell mediates the pruning of branches and spines of neurons (mature dendrite arborization)?
glial cells
• Synaptic increases after birth
density
Synaptic pruning occurs during
adolescence
What plays a significant role in determining synaptic survival?
Activity
Neurogenesis continues on into what decade?
40s
Schizophrenia has been postulated to be associated with excessive synaptic
pruning
What may be responsible for increased synaptic pruning in cases of Schizophrenia?
abnormalities in microglia
What drug has been observed to reduce pruning in patient-derived cell models and can alleviate ?
Minocycline
What disorder, other than schizophrenia, may have deficiencies in synaptic pruning?
Autism spectrum disorder
- As the brain develops, circuits stabilize during critical periods
- Sensory pathways
- Other cognitive functions
Language
What cues control initial specificity of neuronal migration?
Molecular
Once the circuit begins to function, specificity is sharpened through neural
activity
Social deprivation in early childhood is correlated with inreased/decreased incidence of cognitive impairment.
increased
What brain structure can be thin and poorly organized in a socially deprived child ?
Uncinate fasciculus: a structure linked to episodic memory, language, and social/ emotional processing
NOTE: left is healthy, right is not
What brain structure is linked to episodic memory, language, and social/ emotional processing?
Uncinate fasciculus
Some critical periods of development can/cannot be reopened later in life through altered experiences
can
Psychotherapy can help individuals relearn thought patterns, address traumatic experiences, etc.
The Internal Representation of Personal Space Can/ cannot Be Modified by Experience
can
Both brain volume and synaptic density increase/decrease with age
decrease
Decreased brain correlates with cognitive decline (Alzheimer disease)
volume
Density of cortical synapses declines with age but does/does not necessarily result in reverse of function
does not
Adult neurogenesis does occur, and is essential in the formation of?
memory
Long-term can result in growth of new synapses
potentiation
Long-term potentiation in the is essential for memory formation
hippocampus
Hyperstimulation of the presynaptic neuron causes changes in neuron receptor density
Greater number of receptors increases signal sensitivity
LTP induces development on dendrites
postsynaptic
AMPA
spine
What is the neurotrophic hypothesis of depressed states?
Adult neurogenesis is decreased in depressed states
• Successful treatment restores neurotransmitter activity and BDNF release
Enriched environment and physical exercise neurogenesis in the hippocampus
• Possible reason why exercise is helpful under stress or in depressive states
stimulate
cells are the most common type of neuron in the mammalian nervous system
Multipolar
Pyramidal cells are found in the and cerebral cortex
hippocampus
Concerning sensory perception, motor control, and some cognitive functions
- Relay neurons have myelinated, short/long projecting axons
- Local circuit neurons (interneurons) have axons that
long
arborize
What are the predominant neurotransmitters in the brain?
Glutamate and GABA
Glycine is used in spinal cord as an neurotransmitter
inhibitory
What distinct cell body are structure is where dopamine originates?
Dopamine - Ventral Tegmental Area, Substantia Nigra
What distinct cell body structures (nuclei) is where norepinephrine originate?
Locus coeruleus
What distinct cell body structure/es (nuclei) is where seratonin originate?
Serotonin - Raphe nuclei
What distinct cell body structure/es (nuclei) is where acetylcholine originate?
Acetylcholine - Nucleus Basalis of Meynert
(wakefulness) and (hunger) are also significant diffuse neurotransmitter pathways in the brain system
Histamine
orexin
Diffuse NT pathways modulate function of the hierarchical systems which regulati the functions.
global
Receptor activity can mediate action potential (short/long term) and gene expression (short/long term).
short term
long term
