Lecture 1 – Neuroscience Techniques
Psychology focuses on humans. However, neuroscience studies the nervous system in general, so
it doesn’t matter which species we are looking at.
Neural systems are investigated through models:
• Bacteria/yeast cells
e.g., Bacteria don’t have a NS, but are used to express molecules of the NS (e.g., receptors) on their surface. In this way
experiments can be done on the functions of that receptor in such a simple environment, where there is just that one
receptor (no confounds), since the system is so simple.
• Cell culture
studied on a petri dish to discover how cells communicate to each other in a simple system; you can expose them to
antibiotics/neurotransmitters (etc.); you can easily reach them with electrodes.
• Tissue slice
slices of brain tissue kept alive, allowing us to stimulate it by means of electrodes in an
easy and accessible way
• Invertebrates
• Animal
• Human
• Computer
used to simulate neural networks (or molecules of the NS) and how components of the system interact with each other
These are hierarchically organized from simpler systems (lower level of organization) to
complex systems.
These models can be studied in vitro (bacteria, cell culture, tissue slice), in vivo (invertebrates,
animals, humans), or in silico (computers).
Animals in Research
90% are rodents (e.g., rats, mice, hamsters) and less than 1% are more complex animals (e.g.,
dogs, cats, monkeys).
Why are rats so popular? Convenience.
Rats are small (cheap feeding and housing), have short breeding cycles (can easily breed more
rats), have a friendly disposition (easy handling) and are relatively intelligent, agile, and resistant
to infection. Plus, there are many inbred strains available that can help to answer all kinds of
specific RQs and there is a wealth of background data.
1
,Mice are especially popular now because of their convenient genetic manipulation (to understand
how different genes express different molecules, and how these underlie neural transmission).
Rats were more popular before because of their larger brain and consequently easier
manipulation.
More on genetic manipulation on pp. 10
Experimental Techniques
MANIPULATION:
• Lesions
o Mechanical
o Electrolysis
current to coagulate and make very precise lesions
o Chemical
only cells are destroyed, fibers of passage are spared (e.g., ibotenic acid)
• Electrical stimulation
to excite or inhibit neural function via electrodes
• Pharmacological
apply a drug to the system through:
o Osmotic pump
release the drug in a controlled manner over a period of time
o Injection
systemic, intracerebroventricular, or local
o Microdialysis*
• Genetic manipulation
• Behavioral manipulation
expose system to a task and monitor the NS to see how it controls behavior in the task
(motivation by rewarding or aversive stimuli)
2
,MONITORING (measuring):
• In vivo (in the living/intact organism)
o Electrophysiology
record electrical activity
o Microdialysis*
administer drugs to monitor the chemical state of the system
o Behavioral evaluation
how organism responds behaviorally to a task
• Ex vivo
o Localization/Quantification of tissue components in situ (in their original place)
§ Histology
§ Immunohistochemistry
§ In situ hybridization for mRNA or DNA
o Quantification of components in tissue homogenates
(brain yogurt: you make your tissue into a paste turning into a “homogenate”)
§ Genomics
§ Proteomics
§ & a lot more techniques
Closer look at some of these techniques:
• Stereotaxic brain surgery
precise surgical technique for which we need a specific equipment
tailored to the species of interest (e.g., rats, monkeys, humans).
It holds the head of the animal in a fixed position and has arms to
move the tip in three directions (i.e., along the AP, LM, DV axes).
This can be used to do small lesions, lower a microelectrode in the
brain, microinjections, etc.
You use this system in a combination with a stereotaxic brain atlas (which is species-
specific too): it represents the whole brain in the context of a 3D coordinate system with
reference to Bregma or Lambda (visible landmarks on the skull at the point of
intersection between sutures).
You identify where a brain area is relative to the coordinates with the help of the atlas
and use that to move the arm and drill a little hole in correspondence of the target brain
3
, area, in order to lower an electrode or inject a tracer, and then monitor task performance.
• Microdialysis*
The Microdialysis Catheter (probe) is lowered into the brain tissue and consists of an
inner and outer tube.
The probe is inflowed with perfusate (physiological
salt solution) and has a semi-permeable outer
membrane (i.e., water can flow freely in and out while
other molecules cannot). For this reason, it resembles
capillaries (semi-permeable membrane).
Perfusate has the same osmotic value as the brain
tissue: the net inflow and outflow of liquid is zero.
Otherwise, we would either pump liquid into the brain
or extract liquid from the brain, increasing pressure in
the skull (sucking the brain dry or pumping it full of
fluid).
Dialysis is the diffusion of molecules between the
extracellular fluid and the perfusion fluid. In fact,
there is a continuous exchange of compounds, each
flowing from an area of high concentration to an
area of low concentration.
4
Psychology focuses on humans. However, neuroscience studies the nervous system in general, so
it doesn’t matter which species we are looking at.
Neural systems are investigated through models:
• Bacteria/yeast cells
e.g., Bacteria don’t have a NS, but are used to express molecules of the NS (e.g., receptors) on their surface. In this way
experiments can be done on the functions of that receptor in such a simple environment, where there is just that one
receptor (no confounds), since the system is so simple.
• Cell culture
studied on a petri dish to discover how cells communicate to each other in a simple system; you can expose them to
antibiotics/neurotransmitters (etc.); you can easily reach them with electrodes.
• Tissue slice
slices of brain tissue kept alive, allowing us to stimulate it by means of electrodes in an
easy and accessible way
• Invertebrates
• Animal
• Human
• Computer
used to simulate neural networks (or molecules of the NS) and how components of the system interact with each other
These are hierarchically organized from simpler systems (lower level of organization) to
complex systems.
These models can be studied in vitro (bacteria, cell culture, tissue slice), in vivo (invertebrates,
animals, humans), or in silico (computers).
Animals in Research
90% are rodents (e.g., rats, mice, hamsters) and less than 1% are more complex animals (e.g.,
dogs, cats, monkeys).
Why are rats so popular? Convenience.
Rats are small (cheap feeding and housing), have short breeding cycles (can easily breed more
rats), have a friendly disposition (easy handling) and are relatively intelligent, agile, and resistant
to infection. Plus, there are many inbred strains available that can help to answer all kinds of
specific RQs and there is a wealth of background data.
1
,Mice are especially popular now because of their convenient genetic manipulation (to understand
how different genes express different molecules, and how these underlie neural transmission).
Rats were more popular before because of their larger brain and consequently easier
manipulation.
More on genetic manipulation on pp. 10
Experimental Techniques
MANIPULATION:
• Lesions
o Mechanical
o Electrolysis
current to coagulate and make very precise lesions
o Chemical
only cells are destroyed, fibers of passage are spared (e.g., ibotenic acid)
• Electrical stimulation
to excite or inhibit neural function via electrodes
• Pharmacological
apply a drug to the system through:
o Osmotic pump
release the drug in a controlled manner over a period of time
o Injection
systemic, intracerebroventricular, or local
o Microdialysis*
• Genetic manipulation
• Behavioral manipulation
expose system to a task and monitor the NS to see how it controls behavior in the task
(motivation by rewarding or aversive stimuli)
2
,MONITORING (measuring):
• In vivo (in the living/intact organism)
o Electrophysiology
record electrical activity
o Microdialysis*
administer drugs to monitor the chemical state of the system
o Behavioral evaluation
how organism responds behaviorally to a task
• Ex vivo
o Localization/Quantification of tissue components in situ (in their original place)
§ Histology
§ Immunohistochemistry
§ In situ hybridization for mRNA or DNA
o Quantification of components in tissue homogenates
(brain yogurt: you make your tissue into a paste turning into a “homogenate”)
§ Genomics
§ Proteomics
§ & a lot more techniques
Closer look at some of these techniques:
• Stereotaxic brain surgery
precise surgical technique for which we need a specific equipment
tailored to the species of interest (e.g., rats, monkeys, humans).
It holds the head of the animal in a fixed position and has arms to
move the tip in three directions (i.e., along the AP, LM, DV axes).
This can be used to do small lesions, lower a microelectrode in the
brain, microinjections, etc.
You use this system in a combination with a stereotaxic brain atlas (which is species-
specific too): it represents the whole brain in the context of a 3D coordinate system with
reference to Bregma or Lambda (visible landmarks on the skull at the point of
intersection between sutures).
You identify where a brain area is relative to the coordinates with the help of the atlas
and use that to move the arm and drill a little hole in correspondence of the target brain
3
, area, in order to lower an electrode or inject a tracer, and then monitor task performance.
• Microdialysis*
The Microdialysis Catheter (probe) is lowered into the brain tissue and consists of an
inner and outer tube.
The probe is inflowed with perfusate (physiological
salt solution) and has a semi-permeable outer
membrane (i.e., water can flow freely in and out while
other molecules cannot). For this reason, it resembles
capillaries (semi-permeable membrane).
Perfusate has the same osmotic value as the brain
tissue: the net inflow and outflow of liquid is zero.
Otherwise, we would either pump liquid into the brain
or extract liquid from the brain, increasing pressure in
the skull (sucking the brain dry or pumping it full of
fluid).
Dialysis is the diffusion of molecules between the
extracellular fluid and the perfusion fluid. In fact,
there is a continuous exchange of compounds, each
flowing from an area of high concentration to an
area of low concentration.
4
