L.8 Flashcards
What are the three types of ionotropic glutamate receptors?
- NMDA receptors
- AMPA receptors
- Kainate receptors
What is the agonist for NMDA receptors?
NMDA
What is the antagonist for NMDA receptors?
APV drug
What is the agonist for AMPA receptors?
AMPA
What is the antagonist for AMPA receptors?
CNQX drug
What is the agonist for Kainate receptors?
Kainaic acid
What is the antagonist for Kainate receptors?
CNXQ drug
Outline how Non-NMDA Receptors work?
- gluatamte binds to Non-NMDA receptor (activates them)
- when receptors are activated –> ion channels open
- Na+ flow in and K+ flow out
- Na+ influx (more positive)
- EPSP
Outline how NMDA receptors work
- glutamate & glycine must bind to NMDA receptor
- Mg2+ blocks receptor at resting state
- neuron needs to be depolarised to removed Mg2+
- Once Mg2+ is removed, NMDA receptors open = Ca2+ in and K+ out
- Ca2+ acts as secondary messenger causing intracellular processes
What is the role of NMDA receptors in LTP?
- Ca2+ influx is important for synaptic plasticity & long-term potentiation (learning & memory)
What is late EPSP in NMDA receptors
- open more slowly + stay open for longer
- allows a longer-lasting signal
- good for synaptic plasticity & LTP
TRUE or FALSE: NMDA receptors are metabotropic (+ why)
- FALSE (ionotropic)
- they don’t use G-coupled proteins
TRUE or FALSE: Non-NMDA receptors are early-phase EPSP
TRUE
What is the result of too little GABA in the nervous system?
Seizures or muscle spasms due to lack of inhibitory control
What happens when there is too much GABA?
Loss of consciousness and coma
What is the function of the GABAergic system?
Inhibitory signaling to prevent over-excitation
What are the 2 main consequences of NMDA receptors dysregulation
- Schizophrenia
- glutamate excitotoxicity
What is glutamate excitotoxicity
too much glutamate overstimulates neurons
What causes glutamate excitotoxicity to happen
- NMDA receptors are overactivated
- excess Ca2+ influx
What are the effects of glutamate excitotoxicity
- cell damage
- stroke
- seizures
How can NMDA receptors cause Schizophrenia effects
- NMDA receptors are inhibited by PCP
- causes hallucinations like in Schizophrenia
What are the 2 main types of GABA receptors
- GABA ionotropic receptors (GABA A)
- GABA metabotropic receptors (GABA B)
What are the features of GABA ionotropic receptors
- ligand-gated Cl- channels
- fast/early IPSP
What are the features of GABA metabotropic receptors
- G-protein coupled receptors
- slow/late IPSP
- K+ and Ca2+
What happens when two GABA or agonist molecules bind to a GABA receptor?
Cl- channels open
What is the result of Cl⁻ flowing into a neuron?
Hyperpolarization and decreased excitability.
How does the opening of Cl⁻ channels affect excitatory signals?
reduces the effect of excitatory signals
What is the effect of Muscimol on GABA receptors?
- direct agonist
- mimics effect of GABA
What is Bicuculline’s role at the GABA receptor?
- direct antagonist
- blocks/reduces effect of GABA
How do indirect agonists enhance GABAergic activity?
they enhance GABAergic activity without binding to the GABA-binding site
How do benzodiazepines affect GABA receptors?
- increases receptor’s affinity for GABA
- increasing the frequency of channel openings
What are the effects of benzodiazepines?
- relaxes muscles
- reduces anxiety
How do barbiturates affect GABA receptors?
They increase the duration of channel openings when GABA binds
What are the clinical uses of barbiturates?
- anaesthesia
- epilepsy treatment
How does alcohol act on GABA receptors?
Alcohol acts as an agonist at GABA receptors
What effects are seen with low doses of alcohol?
- Mild euphoria
- anxiolytic effects (reduces anxiety)
What effects are seen with higher doses of alcohol?
incoordination and amnesia
What type of protein are GABA metabotropic receptors coupled to?
Gi
What effect does the activation of Gi proteins have on adenylyl cyclase in GABA metabotropic receptors?
It inhibits adenylyl cyclase
How does the activation of GABA metabotropic receptors affect potassium (K+) channels?
It activates K+ channels
What is the result of K+ channel activation in GABA metabotropic receptors?
Hyperpolarization, leading to a late inhibitory post-synaptic potential
What is the therapeutic use of baclofen, which binds to GABA metabotropic receptors?
It helps relax muscles and reduces spasticity (good for Huntington’s disease)
What is the role of glutamate neurons
primary route for sensory and motor information and relay between brain areas
What is the role of GABA neurons
act as interneurons, maintaining a balance between excitation and inhibition
What neurotransmitter is involved in the dopaminergic system?
dopamine
How many major pathways are in the dopaminergic system and what are their names?
- Nigrostriatal
- Mesolimbic
- Mesocortical
- Tuberoinfundibular
What is the main function of the Nigrostriatal Pathway?
motor control (movement)
Where does the Nigrostriatal Pathway project from and to?
From the substantia nigra to the striatum
What diseases are associated with dysfunction in the Nigrostriatal Pathway?
- Parkinson’s Disease
- Huntington’s Disease
What happens to dopamine neurons in Parkinson’s disease?
destruction of dopamine projections from the substantia nigra to the basal ganglia
What happens to dopamine neurons in Huntington’s disease?
destruction of dopamine neurons in the striatum
What treatments are used for diseases associated with the Nigrostriatal Pathway?
- L-Dopa
- MOA inhibitor
- dopamine receptor agonist
How does L-DOPA work in treating Parkinson’s disease?
It converts into dopamine in the brain
What is the role of MAO inhibitors in treating dopaminergic dysfunction?
They prevent the breakdown of dopamine
What do dopamine receptor agonists do?
They mimic dopamine by stimulating dopamine receptors
What is the Mesolimbic Pathway?
Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens
What are the primary functions of the Mesolimbic Pathway?
Rewards, motivation, and addiction (reward system)
What behaviour is associated with dysfunction in the Mesolimbic Pathway?
addictive behaviour
How do drugs affect the Mesolimbic Pathway?
- Drugs hijack the reward system by causing excess dopamine release
- reinforce behaviour and cravings
What are examples of drugs that enhance dopamine release in the Mesolimbic Pathway?
Cocaine and amphetamine
What are the immediate effects of drugs like cocaine and amphetamines?
- mimics sympathetic system (increase blood pressure, heart rate)
- increased alertness
- psychosis and repetitive behaviours
What happens to dopamine transmission with long-term drug use?
- reduced number of dopamine receptors
- less sensitive to dopamine
- more dopamine is needed
- cravings occur reinforcing drug-taking behaviours
How do cocaine and amphetamines affect long-term dopamine levels?
They increase dopamine in pathways, reinforcing drug-taking behaviours
What is the consequence of long-term dopamine stimulation by drugs?
Downregulation of dopamine receptors, leading to cravings for the drug
What is the Mesocortical Pathway
Dopamine projections from the ventral tegmental area (VTA) to the prefrontal cortex
What are the primary functions of the Mesocortical Pathway?
Cognition, including planning, working memory, and learning
What dysfunction is associated with the Mesocortical Pathway?
Psychosis, such as schizophrenia
How does dysfunction in the Mesocortical Pathway affect schizophrenia?
It causes a lack of dopamine, leading to negative symptoms (things missing in behaviour/emotions)
What are negative symptoms
Behaviours and emotions that are reduced or missing compared to a healthy person
What treatments are used to treat dysfunctions in the mesocortical pathway?
Typical antipsychotics and atypical antipsychotics
What do typical antipsychotics like Chlorpromazine and Haloperidol do in the brain?
They block dopamine receptors
How does the brain respond to typical antipsychotics blocking dopamine receptors?
It increases the number of dopamine receptors (upregulation), making the brain more sensitive to dopamine
What are the side effects of typical antipsychotics?
Increased sensitivity to dopamine, which can lead to motor control side effects
How are atypical antipsychotics like Clozapine different from typical antipsychotics?
They target specific dopamine receptors and have fewer motor control side effects
What is the tuberoinfundibular pathway
Dopamine projections from the hypothalamus to the pituitary gland
What is the function of the tuberoinfundibular pathway?
It is involved in endocrine control
How does dopamine affect neurons?
- can produce excitatory signals (EPSP)
- can produce inhibitory signals (IPSP)
What is the effect of D1 dopamine receptors on neurons?
They lead to excitation (EPSPs), increasing neuronal excitability
Which G protein is coupled with D1 receptors?
Gs protein
How do D1 receptors increase neuronal excitability?
- By stimulating adenylyl cyclase and phospholipase C
- leading to excitatory postsynaptic potentials
What is the effect of D2 dopamine receptors on neurons?
They lead to inhibition (IPSPs), decreasing neuronal excitability.
Which G protein is coupled with D2 receptors?
Gi protein
How do D2 receptors decrease neuronal excitability?
- By inhibiting adenylyl cyclase
- opening K+ channels
- closing Ca2+ channels
What is the effect of opening potassium channels through D2 receptor activation?
It hyperpolarizes the neuron, making it less excitable
What is the effect of closing calcium channels through D2 receptor activation?
It decreases calcium influx, which inhibits excitatory signals
Why is the balance between D1 and D2 receptor systems important?
It helps maintain dopaminergic tone in the brain
What conditions can arise from disruptions in the balance between D1 and D2 receptors?
- Parkinson’s disease
- schizophrenia
- addiction
What are the two main pathways of serotonin projections from the Raphe nuclei?
- Ascending pathway
- descending pathway
Describe the descending serotonergic pathway
serotonin projections from the Rpahe nuclei to spinal cord and cerebellum
Describe the ascending pathway of serotonergic system
serotonin projections from the raphe nuclei to cortex and limbic system
What are the primary functions of the serotonergic system?
Mood regulation, sleep, pain, emotion, and appetite control
What are the consequences of dysfunction in the serotonergic system?
Depression and anxiety disorders
What is the overall cause of depression
low serotonin levels
What is the overall cause of anxiety disorders
serotonin imbalance
What are Selective Serotonin Reuptake Inhibitors (SSRIs) and how they work?
medications that treat depression and anxiety disorders by increasing serotonin function by blocking its reuptake
give an example of SSR
fluoxetine/Prozac
What effects does LSD have on the serotonergic system?
LSD acts as a agonist at serotonin receptors in the raphe nucleus and prefrontal cortex, leading to altered sensory perceptions and hallucinogenic properties
Why is depression considered complex regarding serotonin levels?
Depression is not simply due to low serotonin
What is the pathway for noradrenaline projections in the noradrenergic system?
from the lateral coeruleus and project to the thalamus and hypothalamus
What is another way to write serotonin
5HAT
What neurotransmitter is primarily associated with the noradrenergic system?
Norepinephrine (noradrenaline)
What are the key functions of the noradrenergic system?
- attention
- stress response
- mood
- autonomic functions
- cognition
What are the two types of metabotropic receptors in the noradrenergic system?
- Alpha-adrenergic receptors
- Beta-adrenergic receptors
What is the function of Alpha-adrenergic receptors
smooth muscle contraction
What is the function of Beta-adrenergic receptors
relaxation of smooth muscles
What dysfunctions are associated with the noradrenergic system?
- anxiety
- depression
- stress-related disorders
How does overactivity of the noradrenergic system affect a person?
leads to excessive release of noradrenaline, which can result in anxiety
What happens when there is underactivity in the noradrenergic system?
a lack of noradrenaline, which can contribute to various mood disorders
What are beta blockers, and how do they function in the noradrenergic system?
Beta blockers block beta receptors, leading to reduced heart rate and calming the body’s response to stress (e.g., used in anxiety
How do noradrenaline reuptake inhibitors (anti-depressants) work as a treatment?
- prevent reuptake of noradrenaline
- more adrenaline in synaptic cleft
- They increase the levels of noradrenaline in the brain, improving mood and energy (ex: depression)
In which nervous systems does the cholinergic system operate?
PNS and CNS
What role does acetylcholine (ACh) play at the neuromuscular junction?
ACh facilitates communication between motor neurons and skeletal muscles, leading to muscle contraction
How does ACh function in autonomic ganglia?
ACh is involved in the sympathetic and parasympathetic systems, regulating functions such as heart rate and digestion
What are the cholinergic projections in the basal forebrain complex?
from the medial septal nucleus and the nucleus basalis to the hippocampus and cortex
What are the names of 2 cholinergic pathways in the CNS
- basal forebrain complex
- brainstem complex
Where do the 2 cholinergic pathways in the PNS work
- neuromuscular junction
- autonomic ganglia
What is the primary function of the cholinergic pathways in the basal forebrain complex?
memory and cognition
What effect does the loss of ACh neurons in the basal forebrain complex have on memory?
- memory deficits
- Alzheimer’s disease
