2021 Additions Flashcards
Together (the models) provide
complementary and mutually helpful sets of information to - elaborate neural circuitry
NHP models elucidate
the molecular and cellular substrates underlying ASD
NHP assays, in conjunction with
pharmacologic or system-level manipulations (e.g. stimulation) used to advance ASD etiology understanding
NHP models use CRISPR to
disrupt the typical developmental trajectory of neural connectivity and synaptogenesis
Non-human primates are used because
- they have a deep homology in brain circuitry mediating social behaviour and reward
- variation in social behaviour and reward
- reasonable behavioural correlates
- paradigm and therapeutic translation
Dependent variables in NHP assays
- degree of social impairment
- multisensory (audiovisual) integration
- spectrogram of coo vocalisation
- hyper/hypoactivity
TD =
typically developing
What are the NHP behavioural correlates?
- meaningful vocalisations
- mother-offspring bonding
- biparental
- monogamous
- social ecologies
- isomorphic (especially in gametes)
- discriminate between in-group and out-group members
ASC etiology of social
processing
Describe NHP social ecologies
- aggregation into hierarchically organised social groups with dominance status (integration)
- regulate behaviour according to dominance rank
- use visual cues to assess reproductive quality
- social information has intrinsic value
- social interaction is required for normal emotional development
How is a NHP brain similar to human?
- neurons in the auditory cortex and superior temporal sulcus region bind together auditory and visual information in order to provide an integrated representation of social communication
Why are mouse models useful?
- precision and tractability
Give an example of an ethologically relevant measure of pro-sociality in mice
social sniffing displays (there is no obvious analog in humans)
anterior cingulate cortex
- selecting the appropriate behavior based on its anticipated value
- activated during tasks involving mentalizing and self knowledge
amygdala
contributes to tagging emotionally relevant objects in the environment
temporo-parietal regions
perceiving and orienting towards visually salient information
superior temporal sulcus (STS)
responds to a specific type of species-typical vocalization
lateral intraparietal (LIP) region of the macaque
- responds to preceding gaze shifts to a particular region of space
- neural firing enhanced by social gaze
Gaze-following is a precursor to
joint attention
ASC symptoms in NHPs
- perseveration
- ultrasonic vocalisation patterns
- diminished capacity for social responsivity
- STS function is altered responding to visual social cues
perseveration
the repetition of a particular response, regardless of the cessation of a stimulus
NHP practical techniques
- brain-slice in vitro-preparations
- longitudinal or developmental studies
- behavioural assays
- reversal-learning performance in a t-maze
- neural manipulation
- in vivo neuroimaging
- postmortem pathology
- non-invasive eye-tracking
- quantification of reciprocal social interactions
- anatomical tracer injections
- reward allocation test
Give an example of neural manipulation
- intranasal appliactions of oxytocins
tripartite approach
integrating clinical studies in humans, genetic manipulations in mice, and neural systems studies in non human primates
What did Jane Goodall do?
Created a behavioural ethogram demonstrating indices of enriched social repertoire, signifying distinct behavioural correlates and homologies with humans, that suggested the use of NHPs in modelling.
Why Drosophila?
- life cycle of only 12 days; can study 24 generations of this species in a year.
- bear a strong resemblance to human genes a
- small; easy to maintain
- large (hundreds) progeny
- hereditary variants can be distinguished under low-power microscope
- can breed throughout the year
- heteromorphic sex chromosomes
