Neurotransmission/Drugs, Sensory Coding

PSYCH 230 Exam 2

Agonist

Turn ON neurotransmitter system (EPSP or IPSP) —> doesn’t necessarily mean it excites, just that it induces it to do whatever it’s supposed to do

• Presynaptic = release neurotransmitter —> drugs can mimic and cause hyperactivity

• Postsynaptic = activate receptors —> drugs could mimic neurotransmitter, bind to receptor as if and activate 

Antagonist

Turn OFF neurotransmitter system

• Act on synapse in reverse — can be EPSP or IPSP — just inhibits what synapse usually does

  • ex: block calcium to prevent neurotransmitter from being released from vesicles

• Presynaptic = prevent release

• Postsynaptic = block receptors

Inverse agonists

Will act post-synaptically by binding to receptors but inducing opposite effect than what neurotransmitter would

• Causes post-synaptic side to do something different than usual

• Ex: instead of opening sodium channels, will open calcium channels 

Synapse

Where most psychoactive drugs act on

L-Dopa

Presynaptic agonist — activating synapse

• Drug that’s given in Parkinson’s Disease —> associated w death of dopamine cells in substantia nigra, leading to motor impairments

  • Is a precursor of dopamine — cells know how to take molecule and make dopamine out of it

    • Cannot just give dopamine due to BBB — drug is smaller and permeable

Cocaine

Presynaptic agonists — activating synapse

• Drug that inhibits reuptake of dopamine by blocking dopamine transporters

  • Results in dopamine levels increasing (stay in synaptic cleft longer so they bind to receptors more)

Amphetamine

Presynaptic agonists — activating synapse

• Drug that blocks and reverses dopamine transporters

• Increased levels of dopamine and norepinephrine 

• Stimulation, euphoria, wakefulness, improved cognitive control

• Treatment of ADHD and narcolepsy 

Adderall

Prescribed combo of amphetamine and dextroamphetamine, to treat ADHD

SSRIs

Presynaptic agonist — activating synapse

• Block reuptake of serotonin in synapse

• Enhances effect of serotonin

• Commonly prescribed antidepressant - prozac - usually positive effects on mood

Morphine and heroin

Postsynaptic agonists

• Activate postsynaptic opioid receptors

• Euphoric, pain relief — mimics endorphins/emkephalin — amplified effects

Synthetic opioid drugs

Postsynaptic agonists

• Fentanyl: 100x more potent than morphine

• Carfentanil: 100x more potent than fentanyl

• Pain reduction, tranquilizer darts

• Overdose inhibits brainstem breathing circuits (respiratory issues)

Benzodiazepines

Postsynaptic agonist

• Sedative hypnotic, anxiolytic (anti-anxiety), anti-epileptic, muscle relaxant

• Bind to GABA receptors and facilitate GABA effects —> GABA less likely to fire action potential so this drug enhances that effect (causes more inhibition)

  • More hyperpolarization

• Xanax, Valium

Postsynaptic antagonists

Block receptors

• Antipsychotic drugs for schizophrenia

  • Block D2 dopamine receptors on postsynaptic side, preventing dopamine from activating (binding)

    • Because the excess of dopamine in schizophrenia patients cause hallucinations

• “Atypical antipsychotics" — block dopamine AND serotonin receptors 

Oral ingestion, injection, inhalation

The 3 routes of administration for drugs to reach synapse

• Must pass through BBB

Oral ingestion

A route of drug administration

• Cons: longer route (takes longer), digestive system has acids that can break down the drug molecule

• Pros: easiest

Injection

A route of drug administration

• 3 types

  • Subcutaneous - under skin, before muscle

  • Intramuscular - into muscle, closer to blood stream

  • Intravenous - straight into vein, most direct way of administration, retains original concentration of drug

Inhalation

A route of drug administration

• Short pathway — quick effect and at high concentration

Receptor down-regulation

A long term effect/consequence of drug usage

• Development of tolerance to drug —> homeostatic regulation in post-synaptic cell causes receptor degradation

  • After being activated overly chronically, postsynaptic cells have mechanisms to detect that overactivation which isn’t healthy to postsynaptic cell — will degrade some postsynaptic receptors to compensate for the overactivation

  • But people take more - cycle

• Withdrawal in absence —> normal neurotransmitter gives low signal 

Neural sensitization

A long term effect of drug usage

• Becoming hyper-responsible to drug // hypersensitivity to cues (certain places, etc)

• Dopamine sensitization & addiction —> “wanting” vs “liking”

Neurotoxicity

A long term effect of drug usage

• Usually doesn’t cause neurons to die

• Ex: Amphetamine —> kills dopamine neurons from chronic use, but only toxic at 10x street doses

Electrophysiological recording

A technique of measuring action potential

• Intracellular recording measures membrane potential, including spikes

• Extracellular recording measures spikes, but not the membrane potential

Intracellular recording

Access to ongoing membrane potential of the neuron

• We know how much more neg/pos the inside is relative to the outside

• Can record activity w/out action potential

• Done 2 ways:

  • Sharp = penetrate into the interior — just membrane

  • Whole cell path = attach to membrane and break the surface

Extracellular recording

Echo of action potential by placing echo outside cell

• Signal is different by not being enough to record action potential

• Can sense depolarization in the inside by how its mirrored / in opposite direction

Optical recording

A technique of measuring action potential

• Indirect ways that tell us when action potentials happen but without recording electrophysiologically, but instead optically (like a video — only visual)

  • Sodium dependent fluorescent indicators —> calcium does better job

Calcium sensitive dyes

Molecules that become fluorescent in presence of calcium

• Once inside cell, report how much calcium is inside 

  • Aka when action potential is sent, cell will shine —> more calcium = more fluorescence

  • Can record from thousands of neurons using calcium imaging

Sensory coding pathway

Stimulus —> sensation —> perception —> emotion / memory

• Stimulus and sensation = sensory processing

  • Stimulus: physical attributions, can be measured

  • Sensation: how physical attributions around us are presented in brain

• Perception: conscious feeling that their integration gives rise to

Sensation

The activation of sensory brain pathways by a physical stimulus

Perception

The extraction of a mental representation from sensation

• Sensory cues can give rise to different/misleading perceptions —> ex: optical illusions, double images (duck/rabbit)

  • Stimulus and sensation aren’t changing, it’s perception

Psychophysics

How the quantitative aspects of physical stimuli correlate with the perceptions they evoke

Psychometric curve

How we measure perception

• X axis = stimulus intensity, y axis = stimulus detection

Sensory coding

How the quantitative aspects of physical stimuli correlate with the neural activity they evoke

Receptor cells

Specialized cells that respond (electrochemically) to physical sensory stimuli

• Is the trigger that allows sensory stimulus to start entering our NS

  • Their input is not an action potential releasing neurotransmitter (no previous neuron) — it’s the sensory stimulus itself that triggers them

• Found in visual, auditory, olfaction, other modalities —> respond to photons of light, binding of odor molecules

• Convert sensory stimuli into neural signals

• Organism’s perception of the world is dependent on

• Response from cell can evoke a response in synaptically connected neurons — that neuron evokes next response and so on

Spontaneous firing

A sensory neuron occasionally fires spikes with no (obvious) relation to any sensory stimulus

• It is rare for a neuron to have a zero firing rate at baseline - before presenting stimulus, there is firing

• Could be for a reason, but we may not know what — we only have control over the stimulus

• A sensory stimulus can cause the neuron to change its firing rate (increase/decrease)

Raster plot

Graph of when neuron fires per trial at what time

• X axis = time, y axis = trials

• Doesn’t give how, on average, does a neuron respond to stimulus

Peri-stimulus time histogram (PSTH)

Graph of spike rate (shows spontaneous firing rate) vs time

• Gotten by averaging the trials and smoothing graph

• Shows how on average, what the neuron does

• Peri stimulus = around the stimulus; time histogram = the time profile of firing around stimulus time

Selectivity

A sensory neuron will respond to some stimuli and not others

Receptive field

The region of sensory space in which a stimulus will modify the firing of that (single) neuron

• The range of stimuli that cause this neuron to fire (increase firing rate)

• Ex: somatosensory modality responds to mechanical touch — you touch part of receptive field, neuron will fire

Topography

Cortical maps

• Neurons that respond to similar stimuli tend to be close to each other

• Touch information from adjacent parts of the body are represented in adjacent parts in the cortex

Homunculus

Orderly representation of the body in the brain

• Distorted proportions relative to real body proportions 

• Strong correlation with how much of the cortex is dedicated to sense and how much is sensed

• Proportions of cortical somatosensory representations in different species reflect species-specific sensitivity 

Cortical plasticity

Experiences can reshape sensory representations

• After training a monkey to only use 3 fingers, can see shifts in brain

• In amputees, stimulation of face or arm can elicit “phantom limb” sensations