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Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation

View Article: PubMed Central - PubMed

ABSTRACT

Activity in hippocampal area CA1 is essential for consolidating episodic memories, but it is unclear how CA1 activity patterns drive memory formation. We find that in the hours following single-trial contextual fear conditioning (CFC), fast-spiking interneurons (which typically express parvalbumin (PV)) show greater firing coherence with CA1 network oscillations. Post-CFC inhibition of PV+ interneurons blocks fear memory consolidation. This effect is associated with loss of two network changes associated with normal consolidation: (1) augmented sleep-associated delta (0.5–4 Hz), theta (4–12 Hz) and ripple (150–250 Hz) oscillations; and (2) stabilization of CA1 neurons' functional connectivity patterns. Rhythmic activation of PV+ interneurons increases CA1 network coherence and leads to a sustained increase in the strength and stability of functional connections between neurons. Our results suggest that immediately following learning, PV+ interneurons drive CA1 oscillations and reactivation of CA1 ensembles, which directly promotes network plasticity and long-term memory formation.

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Inhibition of PV+ interneurons disrupts the augmentation of CA1 delta and theta oscillations associated with successful CFM consolidation.(a,b) Raw CA1 LFP spectral power in REM and NREM sleep from a representative hM4Di-expressing mouse over the first 6 h post-CFC, following administration of CNO (mean±s.e.m. of 26 local field values from a representative animal; pink circles) versus vehicle (green triangles). (c,e) Post-CFC increases in delta and theta spectral power (from baseline) were present in the first 6 h of post-conditioning sleep in the two control conditions; these increases were blocked by PV+ interneuron inhibition. *indicates P<0.01, Holm–Sidak post hoc test. Mean±s.e.m. shown for LFP values for all animals across a given treatment (hM4-CNO, n=74; hM4-vehicle, n=74; Control-vehicle; n=58). (d,f) Increases in NREM delta and theta power over the first 6 h post CFC were correlated with subsequent CFM consolidation (values indicate mean LFP changes per mouse; Spearman rank order). (g) Representative LFP spectrograms showing spectral power in delta and theta bands across 1,000 s of recording time (matched for time of day) during baseline and in the hours immediately following CFC. In vehicle-treated mice, following CFC there was greater power in delta and theta bands in NREM (bracket) and dramatically increased theta power during REM bouts (filled arrowheads). In CNO-treated mice, there was a suppression of theta in REM bouts (filled arrowheads) as well as a general suppression of 2–12 Hz activity across all states.
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f4: Inhibition of PV+ interneurons disrupts the augmentation of CA1 delta and theta oscillations associated with successful CFM consolidation.(a,b) Raw CA1 LFP spectral power in REM and NREM sleep from a representative hM4Di-expressing mouse over the first 6 h post-CFC, following administration of CNO (mean±s.e.m. of 26 local field values from a representative animal; pink circles) versus vehicle (green triangles). (c,e) Post-CFC increases in delta and theta spectral power (from baseline) were present in the first 6 h of post-conditioning sleep in the two control conditions; these increases were blocked by PV+ interneuron inhibition. *indicates P<0.01, Holm–Sidak post hoc test. Mean±s.e.m. shown for LFP values for all animals across a given treatment (hM4-CNO, n=74; hM4-vehicle, n=74; Control-vehicle; n=58). (d,f) Increases in NREM delta and theta power over the first 6 h post CFC were correlated with subsequent CFM consolidation (values indicate mean LFP changes per mouse; Spearman rank order). (g) Representative LFP spectrograms showing spectral power in delta and theta bands across 1,000 s of recording time (matched for time of day) during baseline and in the hours immediately following CFC. In vehicle-treated mice, following CFC there was greater power in delta and theta bands in NREM (bracket) and dramatically increased theta power during REM bouts (filled arrowheads). In CNO-treated mice, there was a suppression of theta in REM bouts (filled arrowheads) as well as a general suppression of 2–12 Hz activity across all states.

Mentions: To determine how PV+ interneurons coordinate CA1 network activity during memory consolidation, we first characterized changes in CA1 LFP activity over the first 6 h following CFC. LFP power spectra during rapid eye movement (REM) sleep and non-REM (NREM) sleep are shown for a representative hM4Di-expressing mouse in PV+ interneuron inhibition (CNO) and control (vehicle) conditions (Fig. 4a,b; see also Supplementary Fig. 5a). Under control conditions, CA1 spectral power in delta (0.5–4 Hz) and theta (4–12 Hz) frequency bands increased dramatically during post-CFC REM and NREM (but not wake; Supplementary Fig. 5). These changes in spectral power were evident in data averaged across states, although there was some evidence that they waxed and waned across bouts of sleep (Fig. 4g). Delta and theta increases were transient (generally returning to baseline levels after ∼6 h; Supplementary Fig. 5b), and were blocked by CNO administration (Fig. 4c,e, respectively; see also Supplementary Fig. 7). Critically, the degree to which NREM delta and theta activity increased in the first 6 h following CFC predicted individual animal's subsequent behavioural performance (that is, context-specific freezing measured 24 h post CFC; Fig. 4d,f, respectively).


Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation
Inhibition of PV+ interneurons disrupts the augmentation of CA1 delta and theta oscillations associated with successful CFM consolidation.(a,b) Raw CA1 LFP spectral power in REM and NREM sleep from a representative hM4Di-expressing mouse over the first 6 h post-CFC, following administration of CNO (mean±s.e.m. of 26 local field values from a representative animal; pink circles) versus vehicle (green triangles). (c,e) Post-CFC increases in delta and theta spectral power (from baseline) were present in the first 6 h of post-conditioning sleep in the two control conditions; these increases were blocked by PV+ interneuron inhibition. *indicates P<0.01, Holm–Sidak post hoc test. Mean±s.e.m. shown for LFP values for all animals across a given treatment (hM4-CNO, n=74; hM4-vehicle, n=74; Control-vehicle; n=58). (d,f) Increases in NREM delta and theta power over the first 6 h post CFC were correlated with subsequent CFM consolidation (values indicate mean LFP changes per mouse; Spearman rank order). (g) Representative LFP spectrograms showing spectral power in delta and theta bands across 1,000 s of recording time (matched for time of day) during baseline and in the hours immediately following CFC. In vehicle-treated mice, following CFC there was greater power in delta and theta bands in NREM (bracket) and dramatically increased theta power during REM bouts (filled arrowheads). In CNO-treated mice, there was a suppression of theta in REM bouts (filled arrowheads) as well as a general suppression of 2–12 Hz activity across all states.
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Related In: Results  -  Collection

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f4: Inhibition of PV+ interneurons disrupts the augmentation of CA1 delta and theta oscillations associated with successful CFM consolidation.(a,b) Raw CA1 LFP spectral power in REM and NREM sleep from a representative hM4Di-expressing mouse over the first 6 h post-CFC, following administration of CNO (mean±s.e.m. of 26 local field values from a representative animal; pink circles) versus vehicle (green triangles). (c,e) Post-CFC increases in delta and theta spectral power (from baseline) were present in the first 6 h of post-conditioning sleep in the two control conditions; these increases were blocked by PV+ interneuron inhibition. *indicates P<0.01, Holm–Sidak post hoc test. Mean±s.e.m. shown for LFP values for all animals across a given treatment (hM4-CNO, n=74; hM4-vehicle, n=74; Control-vehicle; n=58). (d,f) Increases in NREM delta and theta power over the first 6 h post CFC were correlated with subsequent CFM consolidation (values indicate mean LFP changes per mouse; Spearman rank order). (g) Representative LFP spectrograms showing spectral power in delta and theta bands across 1,000 s of recording time (matched for time of day) during baseline and in the hours immediately following CFC. In vehicle-treated mice, following CFC there was greater power in delta and theta bands in NREM (bracket) and dramatically increased theta power during REM bouts (filled arrowheads). In CNO-treated mice, there was a suppression of theta in REM bouts (filled arrowheads) as well as a general suppression of 2–12 Hz activity across all states.
Mentions: To determine how PV+ interneurons coordinate CA1 network activity during memory consolidation, we first characterized changes in CA1 LFP activity over the first 6 h following CFC. LFP power spectra during rapid eye movement (REM) sleep and non-REM (NREM) sleep are shown for a representative hM4Di-expressing mouse in PV+ interneuron inhibition (CNO) and control (vehicle) conditions (Fig. 4a,b; see also Supplementary Fig. 5a). Under control conditions, CA1 spectral power in delta (0.5–4 Hz) and theta (4–12 Hz) frequency bands increased dramatically during post-CFC REM and NREM (but not wake; Supplementary Fig. 5). These changes in spectral power were evident in data averaged across states, although there was some evidence that they waxed and waned across bouts of sleep (Fig. 4g). Delta and theta increases were transient (generally returning to baseline levels after ∼6 h; Supplementary Fig. 5b), and were blocked by CNO administration (Fig. 4c,e, respectively; see also Supplementary Fig. 7). Critically, the degree to which NREM delta and theta activity increased in the first 6 h following CFC predicted individual animal's subsequent behavioural performance (that is, context-specific freezing measured 24 h post CFC; Fig. 4d,f, respectively).

View Article: PubMed Central - PubMed

ABSTRACT

Activity in hippocampal area CA1 is essential for consolidating episodic memories, but it is unclear how CA1 activity patterns drive memory formation. We find that in the hours following single-trial contextual fear conditioning (CFC), fast-spiking interneurons (which typically express parvalbumin (PV)) show greater firing coherence with CA1 network oscillations. Post-CFC inhibition of PV+ interneurons blocks fear memory consolidation. This effect is associated with loss of two network changes associated with normal consolidation: (1) augmented sleep-associated delta (0.5&ndash;4&thinsp;Hz), theta (4&ndash;12&thinsp;Hz) and ripple (150&ndash;250&thinsp;Hz) oscillations; and (2) stabilization of CA1 neurons' functional connectivity patterns. Rhythmic activation of PV+ interneurons increases CA1 network coherence and leads to a sustained increase in the strength and stability of functional connections between neurons. Our results suggest that immediately following learning, PV+ interneurons drive CA1 oscillations and reactivation of CA1 ensembles, which directly promotes network plasticity and long-term memory formation.

No MeSH data available.


Related in: MedlinePlus