Molecular characterization of Thy1 expressing fear-inhibiting neurons within the basolateral amygdala

نویسندگان

  • Kenneth M McCullough
  • Dennis Choi
  • Jidong Guo
  • Kelsey Zimmerman
  • Jordan Walton
  • Donald G Rainnie
  • Kerry J Ressler
چکیده

Molecular characterization of neuron populations, particularly those controlling threat responses, is essential for understanding the cellular basis of behaviour and identifying pharmacological agents acting selectively on fear-controlling circuitry. Here we demonstrate a comprehensive workflow for identification of pharmacologically tractable markers of behaviourally characterized cell populations. Thy1-eNpHR-, Thy1-Cre- and Thy1-eYFP-labelled neurons of the BLA consistently act as fear inhibiting or 'Fear-Off' neurons during behaviour. We use cell-type-specific optogenetics and chemogenetics (DREADDs) to modulate activity in this population during behaviour to block or enhance fear extinction. Dissociated Thy1-eYFP neurons are isolated using FACS. RNA sequencing identifies genes strongly upregulated in RNA of this population, including Ntsr2, Dkk3, Rspo2 and Wnt7a. Pharmacological manipulation of neurotensin receptor 2 confirms behavioural effects observed in optogenetic and chemogenetic experiments. These experiments identify and validate Ntsr2-expressing neurons within the BLA, as a putative 'Fear-Off' population.

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عنوان ژورنال:

دوره 7  شماره 

صفحات  -

تاریخ انتشار 2016