Restoring Acid-Sensing Ion Channel-1a in the Amygdala of Knock-Out Mice Rescues Fear Memory But Not Unconditioned Fear Responses

Abstract

Acid-sensing ion channel-1a (ASIC1a) contributes to multiple fear behaviors, however the site of ASIC1a action in behavior is not known. To explore a specific location of ASIC1a action, we expressed ASIC1a in the basolateral amygdala of ASIC1a-/-mice using viral vectormediated gene transfer. This rescued context-dependent fear memory, but not the freezing deficit during training or the unconditioned fear response to predator odor. These data pinpoint the basolateral amygdala as the site where ASIC1a contributes to fear memory. They also discriminate fear memory from fear expressed during training and from unconditioned fear. Furthermore, this work illustrates a strategy for identifying discrete brain regions where specific genes contribute to complex behaviors.

The Bed Nucleus of the Stria Terminalis Is Critical for Anxiety-Related Behavior Evoked by CO2 and Acidosis

“…Functional neuroimaging supports amygdala involvement, as both hypercapnia and dyspnea have been suggested to activate the amygdala Liotti et al, 2001;Evans et al, 2002). Further support for the amygdala in CO 2 responses was also provided by recent mouse studies, in which amygdala manipulations altered CO 2 -evoked behavior (Ziemann et al, 2009). However, a 35% CO 2 inhalation challenge surprisingly elicited panic attacks and feelings of fear, anxiety, and panic in human patients with bilateral amygdala lesions (Feinstein et al, 2013).…”

“…Supporting a possible role for the BNST in CO 2 -evoked behavior is the observation that the BNST exhibits relatively dense expression of acid-sensing ion channels (ASICs) (Coryell et al, 2007;, which have been implicated in CO 2 responses (Ziemann et al, 2009). Deleting Asic1a or Asic2 in mice significantly attenuated CO 2 -evoked freezing and CO 2 aversion (Ziemann et al, 2009;.…”

“…Supporting a possible role for the BNST in CO 2 -evoked behavior is the observation that the BNST exhibits relatively dense expression of acid-sensing ion channels (ASICs) (Coryell et al, 2007;, which have been implicated in CO 2 responses (Ziemann et al, 2009). Deleting Asic1a or Asic2 in mice significantly attenuated CO 2 -evoked freezing and CO 2 aversion (Ziemann et al, 2009;. These observations were consistent with previous studies, which found that Asic1a Ϫ/Ϫ and Asic2 Ϫ/Ϫ mice have deficits in fear-and anxiety-related behaviors, such as cued and context fear conditioning and predator odor-evoked freezing (Wemmie et al, 2003;Coryell et al, 2007;; but see Pidoplichko et al, 2014).…”

Acid-Sensing Ion Channels in Neurodegenerative Diseases: Potential Therapeutic Target

“…The loss of ASIC1a also reduces unconditioned fear in the open field test, during acoustic startle, and in response to predator odor (Coryell et al, 2007). Overexpressing ASIC1a, on the other hand, increases fear conditioning , but not unconditioned fear responses (Coryell et al, 2008). Further studies by Wemmie's group suggest that activation of ASIC1a in brain chemosensors contributes to CO 2 induced fear-related behavior ).…”

A Cytosolic Amphiphilic α-Helix Controls the Activity of the Bile Acid-sensitive Ion Channel (BASIC)

“…ASICs are mainly neuronal channels, which are activated by a sudden increase in the extracellular proton concentration (4). They are involved in the sensation of pain and mechanical stimuli, synaptic transmission, and various cognitive processes (5)(6)(7)(8)(9)(10)(11)(12). ENaC is mainly involved in the absorption of Na ϩ in a variety of tissues.…”