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Basolateral amygdala regulation of adult hippocampal neurogenesis and fear-related activation of newborn neurons.

Kirby ED, Friedman AR, Covarrubias D, Ying C, Sun WG, Goosens KA, Sapolsky RM, Kaufer D - Mol. Psychiatry (2011)

Bottom Line: We show that BLA lesions suppress adult neurogenesis, while lesions of the central nucleus of the amygdala do not.Similarly, we show that reducing BLA activity through viral vector-mediated overexpression of an outwardly rectifying potassium channel suppresses neurogenesis.These results demonstrate that BLA activity regulates adult hippocampal neurogenesis and the fear context-specific activation of newborn neurons.

View Article: PubMed Central - PubMed

Affiliation: Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA 94720, USA.

ABSTRACT
Impaired regulation of emotional memory is a feature of several affective disorders, including depression, anxiety and post-traumatic stress disorder. Such regulation occurs, in part, by interactions between the hippocampus and the basolateral amygdala (BLA). Recent studies have indicated that within the adult hippocampus, newborn neurons may contribute to support emotional memory, and that regulation of hippocampal neurogenesis is implicated in depressive disorders. How emotional information affects newborn neurons in adults is not clear. Given the role of the BLA in hippocampus-dependent emotional memory, we investigated whether hippocampal neurogenesis was sensitive to emotional stimuli from the BLA. We show that BLA lesions suppress adult neurogenesis, while lesions of the central nucleus of the amygdala do not. Similarly, we show that reducing BLA activity through viral vector-mediated overexpression of an outwardly rectifying potassium channel suppresses neurogenesis. We also show that BLA lesions prevent selective activation of immature newborn neurons in response to a fear-conditioning task. These results demonstrate that BLA activity regulates adult hippocampal neurogenesis and the fear context-specific activation of newborn neurons. Together, these findings denote functional implications for proliferation and recruitment of new neurons into emotional memory circuits.

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BLA silencing via potassium channel overexpression suppressed neurogenesis(a) Experimental timeline. (b) In rats infused with GFP-Kv1.1 and GFP-only viral vectors to reduce BLA activity (n=8), there were significantly fewer BrdU positive dentate cells ipsilateral to GFP-Kv1.1 infusion. Sham rats, n = 15. *p<0.05. (c) Representative images of GFP expression in virus-infected BLA neurons. Scale bar = 10 μm
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Figure 4: BLA silencing via potassium channel overexpression suppressed neurogenesis(a) Experimental timeline. (b) In rats infused with GFP-Kv1.1 and GFP-only viral vectors to reduce BLA activity (n=8), there were significantly fewer BrdU positive dentate cells ipsilateral to GFP-Kv1.1 infusion. Sham rats, n = 15. *p<0.05. (c) Representative images of GFP expression in virus-infected BLA neurons. Scale bar = 10 μm

Mentions: We next determined whether suppression of neural activity in the BLA without excitotoxic lesion is sufficient to modulate neurogenesis. To reduce BLA neural activity, we ectopically expressed the outwardly rectifying potassium channel Kv1.1 or a GFP-only control from a herpes viral vector in BLA neurons. This transgene construct has been shown to reduce basal neural firing29, 33. GFP-Kv1.1 overexpression reduced proliferative BrdU positive cell number by 36.5% and 30.5% (Figure 4) as compared to GFP-only viral vector infusion and sham-operated controls, respectively. These results indicate that reduction of BLA activity via Kv1.1 overexpression is sufficient to suppress hippocampal neurogenesis ipsilaterally.


Basolateral amygdala regulation of adult hippocampal neurogenesis and fear-related activation of newborn neurons.

Kirby ED, Friedman AR, Covarrubias D, Ying C, Sun WG, Goosens KA, Sapolsky RM, Kaufer D - Mol. Psychiatry (2011)

BLA silencing via potassium channel overexpression suppressed neurogenesis(a) Experimental timeline. (b) In rats infused with GFP-Kv1.1 and GFP-only viral vectors to reduce BLA activity (n=8), there were significantly fewer BrdU positive dentate cells ipsilateral to GFP-Kv1.1 infusion. Sham rats, n = 15. *p<0.05. (c) Representative images of GFP expression in virus-infected BLA neurons. Scale bar = 10 μm
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4310700&req=5

Figure 4: BLA silencing via potassium channel overexpression suppressed neurogenesis(a) Experimental timeline. (b) In rats infused with GFP-Kv1.1 and GFP-only viral vectors to reduce BLA activity (n=8), there were significantly fewer BrdU positive dentate cells ipsilateral to GFP-Kv1.1 infusion. Sham rats, n = 15. *p<0.05. (c) Representative images of GFP expression in virus-infected BLA neurons. Scale bar = 10 μm
Mentions: We next determined whether suppression of neural activity in the BLA without excitotoxic lesion is sufficient to modulate neurogenesis. To reduce BLA neural activity, we ectopically expressed the outwardly rectifying potassium channel Kv1.1 or a GFP-only control from a herpes viral vector in BLA neurons. This transgene construct has been shown to reduce basal neural firing29, 33. GFP-Kv1.1 overexpression reduced proliferative BrdU positive cell number by 36.5% and 30.5% (Figure 4) as compared to GFP-only viral vector infusion and sham-operated controls, respectively. These results indicate that reduction of BLA activity via Kv1.1 overexpression is sufficient to suppress hippocampal neurogenesis ipsilaterally.

Bottom Line: We show that BLA lesions suppress adult neurogenesis, while lesions of the central nucleus of the amygdala do not.Similarly, we show that reducing BLA activity through viral vector-mediated overexpression of an outwardly rectifying potassium channel suppresses neurogenesis.These results demonstrate that BLA activity regulates adult hippocampal neurogenesis and the fear context-specific activation of newborn neurons.

View Article: PubMed Central - PubMed

Affiliation: Helen Wills Neuroscience Institute, University of California-Berkeley, Berkeley, CA 94720, USA.

ABSTRACT
Impaired regulation of emotional memory is a feature of several affective disorders, including depression, anxiety and post-traumatic stress disorder. Such regulation occurs, in part, by interactions between the hippocampus and the basolateral amygdala (BLA). Recent studies have indicated that within the adult hippocampus, newborn neurons may contribute to support emotional memory, and that regulation of hippocampal neurogenesis is implicated in depressive disorders. How emotional information affects newborn neurons in adults is not clear. Given the role of the BLA in hippocampus-dependent emotional memory, we investigated whether hippocampal neurogenesis was sensitive to emotional stimuli from the BLA. We show that BLA lesions suppress adult neurogenesis, while lesions of the central nucleus of the amygdala do not. Similarly, we show that reducing BLA activity through viral vector-mediated overexpression of an outwardly rectifying potassium channel suppresses neurogenesis. We also show that BLA lesions prevent selective activation of immature newborn neurons in response to a fear-conditioning task. These results demonstrate that BLA activity regulates adult hippocampal neurogenesis and the fear context-specific activation of newborn neurons. Together, these findings denote functional implications for proliferation and recruitment of new neurons into emotional memory circuits.

Show MeSH
Related in: MedlinePlus