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Adult hippocampal neurogenesis and pattern separation in DG: a role for feedback inhibition in modulating sparseness to govern population-based coding.

McAvoy K, Besnard A, Sahay A - Front Syst Neurosci (2015)

Bottom Line: The dentate gyrus (DG) of mammals harbors neural stem cells that generate new dentate granule cells (DGCs) throughout life.Behavioral studies using the contextual fear discrimination paradigm have found that selectively augmenting or blocking adult hippocampal neurogenesis enhances or impairs discrimination under conditions of high, but not low, interference suggestive of a role in pattern separation.Here, we propose a role for adult-born DGCs in re-activation coupled modulation of sparseness through feed-back inhibition to govern global remapping in the DG.

View Article: PubMed Central - PubMed

Affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.

ABSTRACT
The dentate gyrus (DG) of mammals harbors neural stem cells that generate new dentate granule cells (DGCs) throughout life. Behavioral studies using the contextual fear discrimination paradigm have found that selectively augmenting or blocking adult hippocampal neurogenesis enhances or impairs discrimination under conditions of high, but not low, interference suggestive of a role in pattern separation. Although contextual discrimination engages population-based coding mechanisms underlying pattern separation such as global remapping in the DG and CA3, how adult hippocampal neurogenesis modulates pattern separation in the DG is poorly understood. Here, we propose a role for adult-born DGCs in re-activation coupled modulation of sparseness through feed-back inhibition to govern global remapping in the DG.

No MeSH data available.


Related in: MedlinePlus

Model illustrating how levels of adult hippocampal neurogenesis dictate population-based coding in DG to minimize interference between engrams of two similar contexts. (A) Context A is made up of features that are unique to context A (A1, A2) and common to contexts A and B (A3, A4). Context B is made up of features that are unique to context B (B1, B2) of which B2 is similar to A1. (B) High levels of neurogenesis: Exposure to context A (time point t1) activates 4–6 weeks adult born DGCs (blue circles). The activation of these 4–6 weeks adult born DGCs recruits feed-back inhibition to increase sparseness in the DG and promotes encoding of features of context A in developmentally born DGCs (brown circles). The engram for context A is made up of adult-born DGCs that have matured (time point t2) and through Hebbian learning and competition for representation have acquired high input specificity for features of context A (green circles with A1 or A2 or A3 or A4) and developmentally born DGCs that encode features of context A (brown circles with A1 or A2 or A3 or A4). (C) High levels of neurogenesis: Exposure to context B re-activates DGCs that have encoded features common to both contexts A and B (Green and brown circles with *A3 or *A4). Re-activation of these DGCs together with activation of 4–6 weeks old adult-born DGCs exerts strong feed-back inhibition onto DG, increases sparseness and promotes encoding of features of context B in individual DGCs. Additionally and importantly, there is lower likelihood that DGCs that have encoded unique features of context A (A1) that are similar to features of context B (B2) are re-activated to encode these features. This results in an engram of context B that has little overlap with engram of context A with the exception of DGCs that encode features common to contexts A and B. (D) Low levels of neurogenesis: Exposure to context A (time point t1) activates a small number of 4–6 weeks adult born DGCs (blue circles). The activation of this reduced number of DGCs recruits less feed-back inhibition, decreases sparseness in the DG and promotes encoding of features of A in many more developmentally born DGCs (brown circles). The engram for context A is made up of adult-born DGCs that have matured (time point t2) and have failed to acquired high input specificity for features of context A (green circles with A1–A2 or A3–A4) and developmentally born DGCs that encode features of context A (brown circles). (E) Exposure to context B re-activates DGCs that have encoded features common to both contexts A and B (Green and brown circles with *A3 or *A4). Furthermore, because of reduced feed-back inhibition recruited by small number of 4–6 weeks old adult-born DGCs and the re-activated mature adult-born DGCs, sparseness in DG is decreased. This, in turn, increases the likelihood that developmentally born DGCs that have encoded features of context A (A1) that are similar to features of context B (B2) are re-activated. Consequently, the engram of context B has significantly more overlap with engram of context A relative to mice with high levels of adult hippocampal neurogenesis.
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Figure 1: Model illustrating how levels of adult hippocampal neurogenesis dictate population-based coding in DG to minimize interference between engrams of two similar contexts. (A) Context A is made up of features that are unique to context A (A1, A2) and common to contexts A and B (A3, A4). Context B is made up of features that are unique to context B (B1, B2) of which B2 is similar to A1. (B) High levels of neurogenesis: Exposure to context A (time point t1) activates 4–6 weeks adult born DGCs (blue circles). The activation of these 4–6 weeks adult born DGCs recruits feed-back inhibition to increase sparseness in the DG and promotes encoding of features of context A in developmentally born DGCs (brown circles). The engram for context A is made up of adult-born DGCs that have matured (time point t2) and through Hebbian learning and competition for representation have acquired high input specificity for features of context A (green circles with A1 or A2 or A3 or A4) and developmentally born DGCs that encode features of context A (brown circles with A1 or A2 or A3 or A4). (C) High levels of neurogenesis: Exposure to context B re-activates DGCs that have encoded features common to both contexts A and B (Green and brown circles with *A3 or *A4). Re-activation of these DGCs together with activation of 4–6 weeks old adult-born DGCs exerts strong feed-back inhibition onto DG, increases sparseness and promotes encoding of features of context B in individual DGCs. Additionally and importantly, there is lower likelihood that DGCs that have encoded unique features of context A (A1) that are similar to features of context B (B2) are re-activated to encode these features. This results in an engram of context B that has little overlap with engram of context A with the exception of DGCs that encode features common to contexts A and B. (D) Low levels of neurogenesis: Exposure to context A (time point t1) activates a small number of 4–6 weeks adult born DGCs (blue circles). The activation of this reduced number of DGCs recruits less feed-back inhibition, decreases sparseness in the DG and promotes encoding of features of A in many more developmentally born DGCs (brown circles). The engram for context A is made up of adult-born DGCs that have matured (time point t2) and have failed to acquired high input specificity for features of context A (green circles with A1–A2 or A3–A4) and developmentally born DGCs that encode features of context A (brown circles). (E) Exposure to context B re-activates DGCs that have encoded features common to both contexts A and B (Green and brown circles with *A3 or *A4). Furthermore, because of reduced feed-back inhibition recruited by small number of 4–6 weeks old adult-born DGCs and the re-activated mature adult-born DGCs, sparseness in DG is decreased. This, in turn, increases the likelihood that developmentally born DGCs that have encoded features of context A (A1) that are similar to features of context B (B2) are re-activated. Consequently, the engram of context B has significantly more overlap with engram of context A relative to mice with high levels of adult hippocampal neurogenesis.

Mentions: Current evidence from studies in mice support differential engagement of feed-back inhibition (Temprana et al., 2015), modulation of DG excitability and sparseness (Ikrar et al., 2013), differences in input specificity (Neunuebel and Knierim, 2012, 2014) and excitability (Schmidt-Hieber et al., 2004; Espósito et al., 2005; Laplagne et al., 2006, 2007; Ge et al., 2007, 2008; Gu et al., 2012) of 4–6 weeks old adult-born DGCs and mature (>6 weeks old) adult-born DGCs). Based on these observations and two recently developed models (Aimone et al., 2011; Kropff et al., 2015; Temprana et al., 2015), we propose that adult-born DGCs contribute to global remapping in DG by expanding the capacity of the DG to encode new information and ensuring high fidelity of re-activation that is coupled with regulation of sparseness through feed-back inhibition. Our model is predicated on two central assumptions. First, the maturation of excitable, immature (4–6 weeks) adult-born DGCs is accompanied by refinement of their synaptic inputs through hebbian learning and competition for neural representation to generate (>4–6 weeks) mature DGCs with high input specificity. The idea is that increasing the number of encoding units available for encoding will promote competition for synaptic inputs and extraction of distinct features to minimize interference (Aimone et al., 2011, 2014; Neunuebel and Knierim, 2012; Kropff et al., 2015; Temprana et al., 2015). Second, limited experimental evidence suggests that adult-born DGCs once mature (>6 weeks of age) are preferentially re-activated by inputs to which they were exposed to when younger (4–6 weeks of age; Tashiro et al., 2007; Aimone et al., 2011). Because the contextual discrimination task in which mice are challenged to discriminate between a training context (Context A) associated with a foot shock and a safe, similar context (Context B; Figure 1A) has been shown to be sensitive to levels of adult hippocampal neurogenesis and involves global remapping in the DG, we will use it to convey our model for how adult-born DGCs contribute to global remapping in the DG. We lead the reader through how changing levels of adult hippocampal neurogenesis affects the engram of context A and context B to dictate the extent of global remapping in the DG (Figure 1).


Adult hippocampal neurogenesis and pattern separation in DG: a role for feedback inhibition in modulating sparseness to govern population-based coding.

McAvoy K, Besnard A, Sahay A - Front Syst Neurosci (2015)

Model illustrating how levels of adult hippocampal neurogenesis dictate population-based coding in DG to minimize interference between engrams of two similar contexts. (A) Context A is made up of features that are unique to context A (A1, A2) and common to contexts A and B (A3, A4). Context B is made up of features that are unique to context B (B1, B2) of which B2 is similar to A1. (B) High levels of neurogenesis: Exposure to context A (time point t1) activates 4–6 weeks adult born DGCs (blue circles). The activation of these 4–6 weeks adult born DGCs recruits feed-back inhibition to increase sparseness in the DG and promotes encoding of features of context A in developmentally born DGCs (brown circles). The engram for context A is made up of adult-born DGCs that have matured (time point t2) and through Hebbian learning and competition for representation have acquired high input specificity for features of context A (green circles with A1 or A2 or A3 or A4) and developmentally born DGCs that encode features of context A (brown circles with A1 or A2 or A3 or A4). (C) High levels of neurogenesis: Exposure to context B re-activates DGCs that have encoded features common to both contexts A and B (Green and brown circles with *A3 or *A4). Re-activation of these DGCs together with activation of 4–6 weeks old adult-born DGCs exerts strong feed-back inhibition onto DG, increases sparseness and promotes encoding of features of context B in individual DGCs. Additionally and importantly, there is lower likelihood that DGCs that have encoded unique features of context A (A1) that are similar to features of context B (B2) are re-activated to encode these features. This results in an engram of context B that has little overlap with engram of context A with the exception of DGCs that encode features common to contexts A and B. (D) Low levels of neurogenesis: Exposure to context A (time point t1) activates a small number of 4–6 weeks adult born DGCs (blue circles). The activation of this reduced number of DGCs recruits less feed-back inhibition, decreases sparseness in the DG and promotes encoding of features of A in many more developmentally born DGCs (brown circles). The engram for context A is made up of adult-born DGCs that have matured (time point t2) and have failed to acquired high input specificity for features of context A (green circles with A1–A2 or A3–A4) and developmentally born DGCs that encode features of context A (brown circles). (E) Exposure to context B re-activates DGCs that have encoded features common to both contexts A and B (Green and brown circles with *A3 or *A4). Furthermore, because of reduced feed-back inhibition recruited by small number of 4–6 weeks old adult-born DGCs and the re-activated mature adult-born DGCs, sparseness in DG is decreased. This, in turn, increases the likelihood that developmentally born DGCs that have encoded features of context A (A1) that are similar to features of context B (B2) are re-activated. Consequently, the engram of context B has significantly more overlap with engram of context A relative to mice with high levels of adult hippocampal neurogenesis.
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Figure 1: Model illustrating how levels of adult hippocampal neurogenesis dictate population-based coding in DG to minimize interference between engrams of two similar contexts. (A) Context A is made up of features that are unique to context A (A1, A2) and common to contexts A and B (A3, A4). Context B is made up of features that are unique to context B (B1, B2) of which B2 is similar to A1. (B) High levels of neurogenesis: Exposure to context A (time point t1) activates 4–6 weeks adult born DGCs (blue circles). The activation of these 4–6 weeks adult born DGCs recruits feed-back inhibition to increase sparseness in the DG and promotes encoding of features of context A in developmentally born DGCs (brown circles). The engram for context A is made up of adult-born DGCs that have matured (time point t2) and through Hebbian learning and competition for representation have acquired high input specificity for features of context A (green circles with A1 or A2 or A3 or A4) and developmentally born DGCs that encode features of context A (brown circles with A1 or A2 or A3 or A4). (C) High levels of neurogenesis: Exposure to context B re-activates DGCs that have encoded features common to both contexts A and B (Green and brown circles with *A3 or *A4). Re-activation of these DGCs together with activation of 4–6 weeks old adult-born DGCs exerts strong feed-back inhibition onto DG, increases sparseness and promotes encoding of features of context B in individual DGCs. Additionally and importantly, there is lower likelihood that DGCs that have encoded unique features of context A (A1) that are similar to features of context B (B2) are re-activated to encode these features. This results in an engram of context B that has little overlap with engram of context A with the exception of DGCs that encode features common to contexts A and B. (D) Low levels of neurogenesis: Exposure to context A (time point t1) activates a small number of 4–6 weeks adult born DGCs (blue circles). The activation of this reduced number of DGCs recruits less feed-back inhibition, decreases sparseness in the DG and promotes encoding of features of A in many more developmentally born DGCs (brown circles). The engram for context A is made up of adult-born DGCs that have matured (time point t2) and have failed to acquired high input specificity for features of context A (green circles with A1–A2 or A3–A4) and developmentally born DGCs that encode features of context A (brown circles). (E) Exposure to context B re-activates DGCs that have encoded features common to both contexts A and B (Green and brown circles with *A3 or *A4). Furthermore, because of reduced feed-back inhibition recruited by small number of 4–6 weeks old adult-born DGCs and the re-activated mature adult-born DGCs, sparseness in DG is decreased. This, in turn, increases the likelihood that developmentally born DGCs that have encoded features of context A (A1) that are similar to features of context B (B2) are re-activated. Consequently, the engram of context B has significantly more overlap with engram of context A relative to mice with high levels of adult hippocampal neurogenesis.
Mentions: Current evidence from studies in mice support differential engagement of feed-back inhibition (Temprana et al., 2015), modulation of DG excitability and sparseness (Ikrar et al., 2013), differences in input specificity (Neunuebel and Knierim, 2012, 2014) and excitability (Schmidt-Hieber et al., 2004; Espósito et al., 2005; Laplagne et al., 2006, 2007; Ge et al., 2007, 2008; Gu et al., 2012) of 4–6 weeks old adult-born DGCs and mature (>6 weeks old) adult-born DGCs). Based on these observations and two recently developed models (Aimone et al., 2011; Kropff et al., 2015; Temprana et al., 2015), we propose that adult-born DGCs contribute to global remapping in DG by expanding the capacity of the DG to encode new information and ensuring high fidelity of re-activation that is coupled with regulation of sparseness through feed-back inhibition. Our model is predicated on two central assumptions. First, the maturation of excitable, immature (4–6 weeks) adult-born DGCs is accompanied by refinement of their synaptic inputs through hebbian learning and competition for neural representation to generate (>4–6 weeks) mature DGCs with high input specificity. The idea is that increasing the number of encoding units available for encoding will promote competition for synaptic inputs and extraction of distinct features to minimize interference (Aimone et al., 2011, 2014; Neunuebel and Knierim, 2012; Kropff et al., 2015; Temprana et al., 2015). Second, limited experimental evidence suggests that adult-born DGCs once mature (>6 weeks of age) are preferentially re-activated by inputs to which they were exposed to when younger (4–6 weeks of age; Tashiro et al., 2007; Aimone et al., 2011). Because the contextual discrimination task in which mice are challenged to discriminate between a training context (Context A) associated with a foot shock and a safe, similar context (Context B; Figure 1A) has been shown to be sensitive to levels of adult hippocampal neurogenesis and involves global remapping in the DG, we will use it to convey our model for how adult-born DGCs contribute to global remapping in the DG. We lead the reader through how changing levels of adult hippocampal neurogenesis affects the engram of context A and context B to dictate the extent of global remapping in the DG (Figure 1).

Bottom Line: The dentate gyrus (DG) of mammals harbors neural stem cells that generate new dentate granule cells (DGCs) throughout life.Behavioral studies using the contextual fear discrimination paradigm have found that selectively augmenting or blocking adult hippocampal neurogenesis enhances or impairs discrimination under conditions of high, but not low, interference suggestive of a role in pattern separation.Here, we propose a role for adult-born DGCs in re-activation coupled modulation of sparseness through feed-back inhibition to govern global remapping in the DG.

View Article: PubMed Central - PubMed

Affiliation: Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.

ABSTRACT
The dentate gyrus (DG) of mammals harbors neural stem cells that generate new dentate granule cells (DGCs) throughout life. Behavioral studies using the contextual fear discrimination paradigm have found that selectively augmenting or blocking adult hippocampal neurogenesis enhances or impairs discrimination under conditions of high, but not low, interference suggestive of a role in pattern separation. Although contextual discrimination engages population-based coding mechanisms underlying pattern separation such as global remapping in the DG and CA3, how adult hippocampal neurogenesis modulates pattern separation in the DG is poorly understood. Here, we propose a role for adult-born DGCs in re-activation coupled modulation of sparseness through feed-back inhibition to govern global remapping in the DG.

No MeSH data available.


Related in: MedlinePlus