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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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Unilateral BLA lesions blocked activation of immature neurons by exposure to a fear-associated context(a) Experimental timeline. (b) Exposure to the fear context (n = 7) resulted in significantly more freezing than exposure to the novel context in sham operated rats (n = 5). (c) Sham-operated rats exposed to the fear context had a greater proportion of BrdU positive cells that co-expressed DCX and cFos. (d) Representative confocal image of a BrdU cell (red) expressing both DCX (blue) and cFos (green). Scale bar = 10 μm. (e) Sham-operated rats exposed to the fear context had similar numbers of cFos+ cells in the dentate gyrus as rats exposed to the novel context. (f) In unilaterally BLA lesioned rats, exposure to the fear context (n = 5) resulted in significantly more freezing than exposure to the novel context (n = 6). (g) In rats exposed to the fear but not the novel context, there was a lower percentage of DCX/cFos labeled BrdU positive cells ipsilateral versus contralateral to the lesion. *p<0.05
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Figure 5: Unilateral BLA lesions blocked activation of immature neurons by exposure to a fear-associated context(a) Experimental timeline. (b) Exposure to the fear context (n = 7) resulted in significantly more freezing than exposure to the novel context in sham operated rats (n = 5). (c) Sham-operated rats exposed to the fear context had a greater proportion of BrdU positive cells that co-expressed DCX and cFos. (d) Representative confocal image of a BrdU cell (red) expressing both DCX (blue) and cFos (green). Scale bar = 10 μm. (e) Sham-operated rats exposed to the fear context had similar numbers of cFos+ cells in the dentate gyrus as rats exposed to the novel context. (f) In unilaterally BLA lesioned rats, exposure to the fear context (n = 5) resulted in significantly more freezing than exposure to the novel context (n = 6). (g) In rats exposed to the fear but not the novel context, there was a lower percentage of DCX/cFos labeled BrdU positive cells ipsilateral versus contralateral to the lesion. *p<0.05

Mentions: Two weeks after labeling proliferative cells with BrdU, rats were exposed to a series of 10 unpredictable shocks in a conditioning chamber (Figure 5a). Re-exposure to the shock-associated context (the fear context) the next day led to greater freezing compared to exposure to a novel context (Figure 5b), indicating robust memory for the fear-associated environment. Forty-five minutes after re-exposure, rats were perfused and assessed for BrdU co-labeling with cFos. BrdU positive cells at this point were 15-19 days old, an age characterized by preferential recruitment into memory networks and possibly enhanced importance for hippocampal memory function18, 34. Using DCX as a marker of immature neurons, we found that exposure to the fear context increased the proportion of BrdU cells co-expressing DCX and cFos compared to rats exposed to the novel context (Figure 5c and d). Exposure to fear context did not alter the total number of cFos-positive cells in the dentate gyrus (Figure 5e). These data suggest that new neurons are activated by fear-associated memory but not simply by exposure to a novel environment.


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 BLA lesions blocked activation of immature neurons by exposure to a fear-associated context(a) Experimental timeline. (b) Exposure to the fear context (n = 7) resulted in significantly more freezing than exposure to the novel context in sham operated rats (n = 5). (c) Sham-operated rats exposed to the fear context had a greater proportion of BrdU positive cells that co-expressed DCX and cFos. (d) Representative confocal image of a BrdU cell (red) expressing both DCX (blue) and cFos (green). Scale bar = 10 μm. (e) Sham-operated rats exposed to the fear context had similar numbers of cFos+ cells in the dentate gyrus as rats exposed to the novel context. (f) In unilaterally BLA lesioned rats, exposure to the fear context (n = 5) resulted in significantly more freezing than exposure to the novel context (n = 6). (g) In rats exposed to the fear but not the novel context, there was a lower percentage of DCX/cFos labeled BrdU positive cells ipsilateral versus contralateral to the lesion. *p<0.05
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4310700&req=5

Figure 5: Unilateral BLA lesions blocked activation of immature neurons by exposure to a fear-associated context(a) Experimental timeline. (b) Exposure to the fear context (n = 7) resulted in significantly more freezing than exposure to the novel context in sham operated rats (n = 5). (c) Sham-operated rats exposed to the fear context had a greater proportion of BrdU positive cells that co-expressed DCX and cFos. (d) Representative confocal image of a BrdU cell (red) expressing both DCX (blue) and cFos (green). Scale bar = 10 μm. (e) Sham-operated rats exposed to the fear context had similar numbers of cFos+ cells in the dentate gyrus as rats exposed to the novel context. (f) In unilaterally BLA lesioned rats, exposure to the fear context (n = 5) resulted in significantly more freezing than exposure to the novel context (n = 6). (g) In rats exposed to the fear but not the novel context, there was a lower percentage of DCX/cFos labeled BrdU positive cells ipsilateral versus contralateral to the lesion. *p<0.05
Mentions: Two weeks after labeling proliferative cells with BrdU, rats were exposed to a series of 10 unpredictable shocks in a conditioning chamber (Figure 5a). Re-exposure to the shock-associated context (the fear context) the next day led to greater freezing compared to exposure to a novel context (Figure 5b), indicating robust memory for the fear-associated environment. Forty-five minutes after re-exposure, rats were perfused and assessed for BrdU co-labeling with cFos. BrdU positive cells at this point were 15-19 days old, an age characterized by preferential recruitment into memory networks and possibly enhanced importance for hippocampal memory function18, 34. Using DCX as a marker of immature neurons, we found that exposure to the fear context increased the proportion of BrdU cells co-expressing DCX and cFos compared to rats exposed to the novel context (Figure 5c and d). Exposure to fear context did not alter the total number of cFos-positive cells in the dentate gyrus (Figure 5e). These data suggest that new neurons are activated by fear-associated memory but not simply by exposure to a novel environment.

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