FEB 27 Flashcards
paper: “__________ control of affective behavioural ______”
CARDIOGENIC control of affective behavioural STATE
paper picks up on question of order/directionality/causality between emotion and behavioural/physiological changes
James-Lange theory of emotion
our subjective feelings are the PERCEPTION of our bodily experience
physiological changes occur BEFORE the experience of emotion
ie. upon noticing your heart rate has increased and feeling yourself running away, you conclude that you’re afraid
background for the paper
emotional states influence bodily physiology (ie. we know that ANXIETY CAUSES INCREASED HR)
whether an increased HR can also CAUSE ANXIETY is UNCLEAR
this has been hard to test - but NEW TECHNIQUES have made it testable
paper makes use of what technical advances?
ChRmine
and tiny mice vest that emits light
ChRmine
highly-sensitive red-shifted channelrhodopsin (increases excitablity)
can target deep tissue
how are they able to target ChRmine only to certain cells?
use a mouse cardiac troponin T promoter (mTNT)
targets virus expressing ChRmine ONLY TO CELLS that express mTNT
these cells = CARDIOMYOCYTES
cardiomyocytes
the cells targeted by this technique
they control the rhythm of the heart
what is meant by ‘non-invasive systemic viral gene delivery’?
inject AAV9 just behind the eye - it diffuses through the system but only has action in the heart
leads to expression of ChRmine in cardiomyocytes throughout the heart
mouse sized LED vest
allows for portable, non-invasive optogenetic simulation of the cardiomyocytes
in vitro validation showed what?
showed that light reliably stimulates the cardiomyocytes
(same thing confirmed in vivo anesthetized mice)
essentially, they first confirmed that they could optogenetically control heart1 rate
details of the optogenetic stimulation that they delivered
induced tachycardia (900 bpm for 500 ms, every 1500 ms)
this mimics non-sustained arrhythmias that are observed in stressful contexts
how did inducing the arrhythmias impact behaviour in the room preference test?
(place mice in box with two rooms - they’re visibly different but neither is more pleasant or aversive than the other)
turn on the stimulation (induce arrhythmia) when they enter one of the rooms
compare to controls
find NO EVIDENCE that the manipulation influenced where mice spend their time
no consistent patterns, mice spend their time in both rooms
room test shows what about the stimulation?
shows that the stimulation alone doesn’t seem to be experienced as pleasurable or aversive in the mice
(if it was, then you’d expect to see them spend their time in the room that’s unassociated with the arrhythmia)
elevated plus maze
elevated cross shape
one arm has no railings, the other does have railings
time in CLOSED versus OPEN ARMS interpreted as measure of ANXIETY-LIKE BEHAVIOUR
less anxiety = more time in open arms
what do they find when they induce arrhythmia in the elevated plus maze?
during stimulation, mice spend less time in open arms of EPM
open field test
time in centre versus periphery is interpreted as measure of anxiety-like behaviour
less anxiety = more time in centre
what do they find when they induce arrhythmia in the open field test?
during stimulation, mice spend less time in centre of OFT
what do they conclude from the behavioural tests?
- increasing heart rate increases anxiety in anxiogenic contexts
(so not in the room preference test, but yes in the other two)
- stimulation alone has no effect - must be elevated HR
(the same manipulation within a baseline heart rate range (660 bpm) had no effect on behaviour
does this generalize to other anxiety tests?
yes
stimulation makes mice more sensitive to shock in a Vogel conflict test
(water restricted mice who get shocked during a percentage of times they lick)
does this involve higher-order brain function?
behaviour experiments suggest that effect of increased HR depends on PERCEIVING the context as STRESSFUL/ANXIETY-PROVOKING
- no effect in RTPP
- anxiety like effect in OFT & EPM
- no effect on pressing for water in absence of shock
- reduced pressing for water with low probability shock
MAY INDICATE INVOLVEMENT OF HIGHER-ORDER BRAIN FUNCTION IN PROCESSING INTEROCEPTIVE CUE OF ELEVATED HR
if higher order brain functions may be involved, then how does increasing HR change brain activity?
increases number of cells active in MANY BRAIN AREAS
particularly interested in PFC bc of higher order brain region hypothesis
activity of what area was found to be required for heart-rate induced-anxiety like behaviour?
posterior insular cortex
in animals where they suppress pIC activity, there’s an attenuated effect of the heightened HR
did they find that PFC activity was required for heart-rate induced anxiety-like behaviour?
no - it wasn’t
there was NO EFFECT when inhibiting PFC acitivity
is inhibition of the posterior insular cortex alone enough to alter anxiety like behaviour?
no
inhibiting the posterior insular cortex doesn’t inhibit anxiety
