Anxiety Flashcards
• Babeev et al (2018):
. Show that deletion of IgSF9b (a cell adhesion molecule) in mice normalises anxiety behaviours (and in pathologically anxious mice Nlgn KO) and so suggests that IgSF9b is a key regulator of inhibition in the amygdala and that IgSF9b-expressing synapses in CeM may represent a target for anxiolytic therapies. Deletion of IgSF9b in the CeM results in enhancement of inhibitory synaptic transmission
• Herry et al (2008)
): In vivo single unit recordings and pharmacological inactivation with muscimol (GABAAR agonist) in behaving mice using a discriminatory auditory fear conditioning paradigm. Found that paired CS and US resulted in enhanced firing of population of BL amygdala neurons (fearneurons) when animals are subsequently exposed to CS alone and after extinction these neurons no longer fire to the CS and another set of neurons (extinction neurons) emerged which selectively respond to the S undergoing extinction. Infusion of muscimol into the BA to inactivate the neurons impaired both extinction and fear renewal. When onto stimulate the mPFC and HC and found that fear neurons fear neurons receive input from the HC and project to mPFC whereas extinction neurons connected to mPFC in both directions. Change in firing to extinction firing precedes the behavioural shift and suggests that switching between distinct behavioural states can be triggered by selective activation of specific neuronal circuits integrating sensory and contextual information
• Likhtik et al(2008):
Lesion ICM neurons by lesioning them with toxin that selectively targets cells expressing micro-opioid receptors (microORs) and find following fear conditioning and extinction in rats that with a decrease in ICM neurons. Extinguished fear responses can be reactivated, suggesting that these neurons are required for the expression of learned extinction. The expression of extinction correlated negatively with the number of surviving IMC neurons
o Didn’t reduce all the cells.
• Squires and Braestrup (1977)
KI mutation of α1 into the GABAAR in germline mice and tested on elevated plus maze and rotarod and mice failed to show the sedative effect, amnesiac and partly the anticonvulsant actions of diazepam whereas anxiolytic effects were fully retained suggesting α1 has sedative property
• Rudolph et al (1999):
KI mutation of α1 into the GABAAR in germline mice and tested on elevated plus maze and rotarod and mice failed to show the sedative effect, amnesiac and partly the anticonvulsant actions of diazepam whereas anxiolytic effects were fully retained suggesting α1 has sedative property
• Low et al (2000)
• Point mutation in α2 and α3 in GABAA and assessed anxiety e.g. with elevated plus maze and found that anxiolytic action of diazepam was absent in α2 KI but not α3 but still showed sedative and motor impairment effects. Could be potential treatment for anxiety
• Christian et al (2013):
Used KO of the dbi gene → mouse brain slices, patch clamping and GABA uncaging in the thalamus and found a endogenous potentiation of GABAergic transmission and responses to GABA uncaging in the thalamic reticular nucleus (nRT), in mice with dbi gene deleted, and mice in with BZ binding to α3 subunit containing GABAR is disrupted. Viral transduction of DBI into nRT is sufficient to rescue the endogenous potentiation in dbi gene deleted mice. Together these results indicate that DBI mediates endogenous nucleus-specific BZ-mimicking roles to modulate nRT function and suppress thalamocortical oscillations
• Ujjainwala et al(2017)
Showed that dbi KO mice exhibit reduced social interest and also lack the sex difference in social interest levels observed in wt mice, in which males showed higher social interest levels and females
• Gueze et al (2007):
Using PET with [11C]flumazenil to compare GABA binding in veterans with or without PSTD and found that there was a lower expression of GABAAR in PTSD patients, throughout the cortex, hippocampis and thalamus
• McCall et al (2015):
Using a mixture of in vivo optogenetics, chemogenetics and retrograde tracing, determine that increased tonic activity of the LC-NE system is necessary and sufficient to induce stress-induced anxiey with behavioural tests on mice such as elevated zero maze and open field test. Selective inhibiton for example during stress prevented subsequent anxiety-like behaviour. So appears that NA is a critical mediator of acute stress induced anxiety
• McCall et al 2017
Optogenetic manipulation of LC-NA inputs into the BLA and found that release NE (fast scan cyclic voltammetry) and evoked down stream modulation in BLA neurons that project to anxiogenic brain regions. Stimulation of the fibres sufficient to induce conditioned aversion and stimulation induced increase in NA tone is sufficient to produce anxiety-like behaviour
• Kindt et al (2009):
Humans Measured potentiation of eyeblink startle reflex to a loud noise and reconsolidation of fear memory was manipulated administration of propranolol (β blocker). Found that oral administration before reactivation of fear memory resulted in substantial weakening of fear response 24 hours later and that reinstatement fails to uncover any fear response suggesting that the fear memory may either be erased or may be unavailable as a result of retrieval failure
o Controversial
• Guistino et al (2017):
Auditory fear conditioning in rats and then either immediate or delayed extinction training. Propranolol infusion into the BLA of mPFC. Showed that propranolol rescues the IED in BLA infusion suggesting that heightened NA activity in the BLA underlies stress induced extinction deficit
• Villain et al (2018):
: Mice with pre or post-natal stress tested on fear conditioning, ‘city-like’ paradigm (model for PTSD). After reactivation mice receive propranolol during reconsolidation. Control mice strongly avoid the shock compartment and compartments containing cues associated with the electric shock and injection of propranolol reduced the memory of traumatic event. This effect of propranolol was not present in pre-or post-natal stress mice indicating that early stress exposure may have impact on propranolol PTSD treatment outcomes.
• Ohmura et al (2014):
animal plus maze and optogenetic activation of 5HT neurons and found that activation of 5HT neurons in the median raphe nucleus was correlated to enhanced anxiety like behaviours in mice and not the dorsal RN. Indicate that an acute increase in 5HT enhances anxiety
