Limits...
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.

Show MeSH

Related in: MedlinePlus

Unilateral lesions of the BLA, but not the CeA, ipsilaterally suppressed neurogenesis(a) Experimental timeline. (b) There were significantly fewer dentate PCNA positive cells ipsilateral versus contralateral to unilateral BLA lesion (n = 5). Similar suppression of PCNA positive cells was found with bilateral BLA lesion (n = 6) as ipsilateral to unilateral lesion. The number of PCNA positive cells contralateral to lesion was similar to that found in the dentate gyrus of bilateral sham-operated animals (n = 3) and no surgery rats (n = 4). *p<0.05. (c) In BLA (n = 5), but not CeA (n = 6) lesioned rats, there were significantly fewer BrdU positive dentate cells ipsilateral versus contralateral to the lesion. Sham rats, n = 6. *p<0.01. (d) In BLA (n = 5), but not CeA (n = 6) lesioned rats, there were significantly fewer PCNA positive cells ipsilateral versus contralateral to the lesion. Sham rat, n = 6. *p<0.01.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4310700&req=5

Figure 3: Unilateral lesions of the BLA, but not the CeA, ipsilaterally suppressed neurogenesis(a) Experimental timeline. (b) There were significantly fewer dentate PCNA positive cells ipsilateral versus contralateral to unilateral BLA lesion (n = 5). Similar suppression of PCNA positive cells was found with bilateral BLA lesion (n = 6) as ipsilateral to unilateral lesion. The number of PCNA positive cells contralateral to lesion was similar to that found in the dentate gyrus of bilateral sham-operated animals (n = 3) and no surgery rats (n = 4). *p<0.05. (c) In BLA (n = 5), but not CeA (n = 6) lesioned rats, there were significantly fewer BrdU positive dentate cells ipsilateral versus contralateral to the lesion. Sham rats, n = 6. *p<0.01. (d) In BLA (n = 5), but not CeA (n = 6) lesioned rats, there were significantly fewer PCNA positive cells ipsilateral versus contralateral to the lesion. Sham rat, n = 6. *p<0.01.

Mentions: We next investigated whether the suppression of adult hippocampal neurogenesis following BLA lesion is mediated by ipsilateral neural connections or by possible systemic changes (such as a change in circulating hormone levels). Because ipsilateral connections mediate the influence of BLA activity on hippocampal LTP10, 32, we predicted that BLA lesion-induced suppression of adult hippocampal neurogenesis would similarly rely on ipsilateral neural connections and be hemisphere-specific. To investigate this hypothesis, BrdU and PCNA positive cells were quantified three weeks following unilateral BLA lesion (Figure 3a).


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)

Unilateral lesions of the BLA, but not the CeA, ipsilaterally suppressed neurogenesis(a) Experimental timeline. (b) There were significantly fewer dentate PCNA positive cells ipsilateral versus contralateral to unilateral BLA lesion (n = 5). Similar suppression of PCNA positive cells was found with bilateral BLA lesion (n = 6) as ipsilateral to unilateral lesion. The number of PCNA positive cells contralateral to lesion was similar to that found in the dentate gyrus of bilateral sham-operated animals (n = 3) and no surgery rats (n = 4). *p<0.05. (c) In BLA (n = 5), but not CeA (n = 6) lesioned rats, there were significantly fewer BrdU positive dentate cells ipsilateral versus contralateral to the lesion. Sham rats, n = 6. *p<0.01. (d) In BLA (n = 5), but not CeA (n = 6) lesioned rats, there were significantly fewer PCNA positive cells ipsilateral versus contralateral to the lesion. Sham rat, n = 6. *p<0.01.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4310700&req=5

Figure 3: Unilateral lesions of the BLA, but not the CeA, ipsilaterally suppressed neurogenesis(a) Experimental timeline. (b) There were significantly fewer dentate PCNA positive cells ipsilateral versus contralateral to unilateral BLA lesion (n = 5). Similar suppression of PCNA positive cells was found with bilateral BLA lesion (n = 6) as ipsilateral to unilateral lesion. The number of PCNA positive cells contralateral to lesion was similar to that found in the dentate gyrus of bilateral sham-operated animals (n = 3) and no surgery rats (n = 4). *p<0.05. (c) In BLA (n = 5), but not CeA (n = 6) lesioned rats, there were significantly fewer BrdU positive dentate cells ipsilateral versus contralateral to the lesion. Sham rats, n = 6. *p<0.01. (d) In BLA (n = 5), but not CeA (n = 6) lesioned rats, there were significantly fewer PCNA positive cells ipsilateral versus contralateral to the lesion. Sham rat, n = 6. *p<0.01.
Mentions: We next investigated whether the suppression of adult hippocampal neurogenesis following BLA lesion is mediated by ipsilateral neural connections or by possible systemic changes (such as a change in circulating hormone levels). Because ipsilateral connections mediate the influence of BLA activity on hippocampal LTP10, 32, we predicted that BLA lesion-induced suppression of adult hippocampal neurogenesis would similarly rely on ipsilateral neural connections and be hemisphere-specific. To investigate this hypothesis, BrdU and PCNA positive cells were quantified three weeks following unilateral BLA lesion (Figure 3a).

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