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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.

No MeSH data available.


Coherence changes in CA1 neurons during CFM consolidation.(a,b) Experimental paradigm. Male C57BL/6J mice were recorded for a 24-h baseline period in their home cage, starting at lights-on, after which they either underwent single-trial CFC in a novel recording chamber (a) or sham training (b) (n=5 mice per group). Afterward, all mice were returned to their home cage for an additional 24 h of recording. Context-specific freezing was assessed as a measure of CFM consolidation 24 h later. (c,d) Coherent firing is shown for three representative FS interneurons (c) and three representative principal neurons from the same site (d) recorded in CA1 over the first 6 h of baseline (black) or the first 6 h following either CFC or sham conditioning (red or purple, respectively). Coherent firing is shown separately for periods of NREM, REM and wake. (e) Quantification of post-CFC changes in delta and theta coherence (from baseline) for FS interneurons and principal neurons. Box plots indicate 25th, 50th and 75th percentile values. ↑↓ indicates relative increases or decreases of P<0.05 for post CFC or post Sham versus baseline, Wilcoxon signed rank test. (f) Mean (±s.e.m.) frequency of SPWR events for CFC and Sham mice during the first 6 h of baseline recording, and following CFC or sham conditioning. ↑ indicates relative increase of P<0.05 for post CFC versus baseline, *indicates P<0.05 post CFC versus post Sham, Holm-Sidak post hoc test. (g) Mean (±s.e.m.) firing rate changes (from baseline values) during SPWR events. *indicates P<0.05 post CFC versus post Sham, Holm–Sidak post hoc test.
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f1: Coherence changes in CA1 neurons during CFM consolidation.(a,b) Experimental paradigm. Male C57BL/6J mice were recorded for a 24-h baseline period in their home cage, starting at lights-on, after which they either underwent single-trial CFC in a novel recording chamber (a) or sham training (b) (n=5 mice per group). Afterward, all mice were returned to their home cage for an additional 24 h of recording. Context-specific freezing was assessed as a measure of CFM consolidation 24 h later. (c,d) Coherent firing is shown for three representative FS interneurons (c) and three representative principal neurons from the same site (d) recorded in CA1 over the first 6 h of baseline (black) or the first 6 h following either CFC or sham conditioning (red or purple, respectively). Coherent firing is shown separately for periods of NREM, REM and wake. (e) Quantification of post-CFC changes in delta and theta coherence (from baseline) for FS interneurons and principal neurons. Box plots indicate 25th, 50th and 75th percentile values. ↑↓ indicates relative increases or decreases of P<0.05 for post CFC or post Sham versus baseline, Wilcoxon signed rank test. (f) Mean (±s.e.m.) frequency of SPWR events for CFC and Sham mice during the first 6 h of baseline recording, and following CFC or sham conditioning. ↑ indicates relative increase of P<0.05 for post CFC versus baseline, *indicates P<0.05 post CFC versus post Sham, Holm-Sidak post hoc test. (g) Mean (±s.e.m.) firing rate changes (from baseline values) during SPWR events. *indicates P<0.05 post CFC versus post Sham, Holm–Sidak post hoc test.

Mentions: To characterize the dynamic response of CA1 neurons to newly learned information, we continuously recorded the firing of FS interneurons and non-FS (presumptive principal) neurons in wild-type mice during CFM consolidation, using chronically implanted stereotrode arrays (Supplementary Figs 1 and 2). Following a 24-h baseline recording period (during which CA1 neuronal and local field potential (LFP) activity was recorded continuously), C57BL/6J mice underwent single-trial CFC or sham conditioning. Recording continued over the next 24 h to assess changes in neuronal and network activity associated with CFM consolidation (Fig. 1a,b). FS interneurons (identified based on characteristically narrow spike waveform) showed dramatically increased spike-field coherence in the first 6 h following CFC, but not following sham conditioning (Fig. 1c)2223. Similarly, neighbouring principal neurons showed greater spike-field coherence following CFC, but not sham conditioning (Fig. 1d). These changes were evident for both delta- and theta-frequency oscillatory activity in CA1, across behavioural states (Fig. 1e), and were not due to changes in post-CFC sleep architecture (Supplementary Fig. 3). These data suggest that rhythmic synchrony of neuronal firing in the CA1 network is augmented during active memory consolidation. Neuronal firing was also altered during SPWR events following CFC (Fig. 1f,g). While no change in spike-field coherence was detected during ripple oscillations, following CFC there was an increase in both the overall frequency of SPWR events (Fig. 1f) and FS interneuron firing rates during SPWRs (Fig. 1g).


Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation
Coherence changes in CA1 neurons during CFM consolidation.(a,b) Experimental paradigm. Male C57BL/6J mice were recorded for a 24-h baseline period in their home cage, starting at lights-on, after which they either underwent single-trial CFC in a novel recording chamber (a) or sham training (b) (n=5 mice per group). Afterward, all mice were returned to their home cage for an additional 24 h of recording. Context-specific freezing was assessed as a measure of CFM consolidation 24 h later. (c,d) Coherent firing is shown for three representative FS interneurons (c) and three representative principal neurons from the same site (d) recorded in CA1 over the first 6 h of baseline (black) or the first 6 h following either CFC or sham conditioning (red or purple, respectively). Coherent firing is shown separately for periods of NREM, REM and wake. (e) Quantification of post-CFC changes in delta and theta coherence (from baseline) for FS interneurons and principal neurons. Box plots indicate 25th, 50th and 75th percentile values. ↑↓ indicates relative increases or decreases of P<0.05 for post CFC or post Sham versus baseline, Wilcoxon signed rank test. (f) Mean (±s.e.m.) frequency of SPWR events for CFC and Sham mice during the first 6 h of baseline recording, and following CFC or sham conditioning. ↑ indicates relative increase of P<0.05 for post CFC versus baseline, *indicates P<0.05 post CFC versus post Sham, Holm-Sidak post hoc test. (g) Mean (±s.e.m.) firing rate changes (from baseline values) during SPWR events. *indicates P<0.05 post CFC versus post Sham, Holm–Sidak post hoc test.
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f1: Coherence changes in CA1 neurons during CFM consolidation.(a,b) Experimental paradigm. Male C57BL/6J mice were recorded for a 24-h baseline period in their home cage, starting at lights-on, after which they either underwent single-trial CFC in a novel recording chamber (a) or sham training (b) (n=5 mice per group). Afterward, all mice were returned to their home cage for an additional 24 h of recording. Context-specific freezing was assessed as a measure of CFM consolidation 24 h later. (c,d) Coherent firing is shown for three representative FS interneurons (c) and three representative principal neurons from the same site (d) recorded in CA1 over the first 6 h of baseline (black) or the first 6 h following either CFC or sham conditioning (red or purple, respectively). Coherent firing is shown separately for periods of NREM, REM and wake. (e) Quantification of post-CFC changes in delta and theta coherence (from baseline) for FS interneurons and principal neurons. Box plots indicate 25th, 50th and 75th percentile values. ↑↓ indicates relative increases or decreases of P<0.05 for post CFC or post Sham versus baseline, Wilcoxon signed rank test. (f) Mean (±s.e.m.) frequency of SPWR events for CFC and Sham mice during the first 6 h of baseline recording, and following CFC or sham conditioning. ↑ indicates relative increase of P<0.05 for post CFC versus baseline, *indicates P<0.05 post CFC versus post Sham, Holm-Sidak post hoc test. (g) Mean (±s.e.m.) firing rate changes (from baseline values) during SPWR events. *indicates P<0.05 post CFC versus post Sham, Holm–Sidak post hoc test.
Mentions: To characterize the dynamic response of CA1 neurons to newly learned information, we continuously recorded the firing of FS interneurons and non-FS (presumptive principal) neurons in wild-type mice during CFM consolidation, using chronically implanted stereotrode arrays (Supplementary Figs 1 and 2). Following a 24-h baseline recording period (during which CA1 neuronal and local field potential (LFP) activity was recorded continuously), C57BL/6J mice underwent single-trial CFC or sham conditioning. Recording continued over the next 24 h to assess changes in neuronal and network activity associated with CFM consolidation (Fig. 1a,b). FS interneurons (identified based on characteristically narrow spike waveform) showed dramatically increased spike-field coherence in the first 6 h following CFC, but not following sham conditioning (Fig. 1c)2223. Similarly, neighbouring principal neurons showed greater spike-field coherence following CFC, but not sham conditioning (Fig. 1d). These changes were evident for both delta- and theta-frequency oscillatory activity in CA1, across behavioural states (Fig. 1e), and were not due to changes in post-CFC sleep architecture (Supplementary Fig. 3). These data suggest that rhythmic synchrony of neuronal firing in the CA1 network is augmented during active memory consolidation. Neuronal firing was also altered during SPWR events following CFC (Fig. 1f,g). While no change in spike-field coherence was detected during ripple oscillations, following CFC there was an increase in both the overall frequency of SPWR events (Fig. 1f) and FS interneuron firing rates during SPWRs (Fig. 1g).

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.