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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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Coherent firing induced by optogenetic stimulation of PV+ interneurons increases CA1 network stability and connection strength.(a) Perievent firing rasters (top) and perievent firing histograms (bottom) for a representative CA1 FS interneuron and three neighbouring principal neurons recorded from a Pvalb-IRES-CRE mouse expressing ChR2. Firing is shown over 250 s of recording before and during rhythmic (8 Hz) 473 nm light stimulation of PV+ interneurons. (b) A representative 5 s LFP trace (left) and perievent LFP raster (right) for one of the recording sites from a in baseline and stimulation conditions. (c) Changes in spike-field coherence (from baseline) induced by various frequencies of rhythmic PV+ interneuron stimulation in virally transduced neurons. Significant increases (from baseline) were present at stimulation frequencies between 4 and 10 Hz. #indicates P<0.05, Wilcoxon signed rank test. (d) Across 4–10 Hz stimulation frequencies, changes in spike-field coherence predicted changes in stability of functional connectivity for individual neurons (Spearmann rank order, n=320 neurons). (e) Comparison of CA1 spike-field coherence across a 30-min baseline period, 30 min of 7 Hz stimulation, and 2 h or post-stimulation recovery, in mice with CA1 transduction of ChR2 (blue) or GFP (black). (f) Over the 2 h following 7 Hz stimulation, CA1 neuronal functional connectivity in mice transduced with ChR2 showed an increase in stability relative to baseline. For (c,d), #indicates P<0.05, Wilcoxon signed rank test. For (c,e,f), all values indicate mean±s.e.m. (g) Neuronal functional connectivity strength also showed an increase in ChR2-transduced mice following 7 Hz stimulation. A similar change that was not seen in GFP-transduced mice. P value indicates results of Kolmogorov–Smirnov test.
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f8: Coherent firing induced by optogenetic stimulation of PV+ interneurons increases CA1 network stability and connection strength.(a) Perievent firing rasters (top) and perievent firing histograms (bottom) for a representative CA1 FS interneuron and three neighbouring principal neurons recorded from a Pvalb-IRES-CRE mouse expressing ChR2. Firing is shown over 250 s of recording before and during rhythmic (8 Hz) 473 nm light stimulation of PV+ interneurons. (b) A representative 5 s LFP trace (left) and perievent LFP raster (right) for one of the recording sites from a in baseline and stimulation conditions. (c) Changes in spike-field coherence (from baseline) induced by various frequencies of rhythmic PV+ interneuron stimulation in virally transduced neurons. Significant increases (from baseline) were present at stimulation frequencies between 4 and 10 Hz. #indicates P<0.05, Wilcoxon signed rank test. (d) Across 4–10 Hz stimulation frequencies, changes in spike-field coherence predicted changes in stability of functional connectivity for individual neurons (Spearmann rank order, n=320 neurons). (e) Comparison of CA1 spike-field coherence across a 30-min baseline period, 30 min of 7 Hz stimulation, and 2 h or post-stimulation recovery, in mice with CA1 transduction of ChR2 (blue) or GFP (black). (f) Over the 2 h following 7 Hz stimulation, CA1 neuronal functional connectivity in mice transduced with ChR2 showed an increase in stability relative to baseline. For (c,d), #indicates P<0.05, Wilcoxon signed rank test. For (c,e,f), all values indicate mean±s.e.m. (g) Neuronal functional connectivity strength also showed an increase in ChR2-transduced mice following 7 Hz stimulation. A similar change that was not seen in GFP-transduced mice. P value indicates results of Kolmogorov–Smirnov test.

Mentions: We next tested whether rhythmic PV+ interneuron activity is sufficient to augment CA1 oscillations and stabilize CA1 ensembles. To do this, we recorded network dynamics among CA1 neurons before, during, and after rhythmic optogenetic stimulation of PV+ interneurons in anaesthetized animals (Supplementary Fig. 12). In transgenic mice expressing Channelrhodopsin 2 (ChR2) in PV+ interneurons (PV:ChR2), stimulation across a range of frequencies led to rhythmic activation of FS interneurons, and rhythmic inhibition of neighbouring principal neurons (Supplementary Fig. 13a). Stimulation also led to frequency-specific, rhythmic activity in the CA1 LFP and enhanced neuronal spike-field coherence at the stimulation frequency (Supplementary Fig. 13a; Supplementary Fig. 15a). In contrast, stimulation above (18 Hz) or below (2 Hz) this range had relatively modest effects on spike-field coherence. Because PV-expressing interneurons outside CA1 can contribute to CA1 network oscillations32, we repeated these experiments in AAV-transduced Pvalb-IRES-CRE transgenic mice with CA1-targeted expression of ChR2. In these mice, rhythmic PV+ interneuron activation led to similar increases in CA1 rhythmic firing and LFP rhythmicity (Fig. 8a,b and Supplementary Fig. 14). This was true both under anaesthetized conditions (Fig. 8) and in awake, behaving mice (Supplementary Fig. 16). Again, the strongest effects on spike-field coherence were seen for stimulation frequencies between 4 and 10 Hz (Fig. 8c).


Parvalbumin-expressing interneurons coordinate hippocampal network dynamics required for memory consolidation
Coherent firing induced by optogenetic stimulation of PV+ interneurons increases CA1 network stability and connection strength.(a) Perievent firing rasters (top) and perievent firing histograms (bottom) for a representative CA1 FS interneuron and three neighbouring principal neurons recorded from a Pvalb-IRES-CRE mouse expressing ChR2. Firing is shown over 250 s of recording before and during rhythmic (8 Hz) 473 nm light stimulation of PV+ interneurons. (b) A representative 5 s LFP trace (left) and perievent LFP raster (right) for one of the recording sites from a in baseline and stimulation conditions. (c) Changes in spike-field coherence (from baseline) induced by various frequencies of rhythmic PV+ interneuron stimulation in virally transduced neurons. Significant increases (from baseline) were present at stimulation frequencies between 4 and 10 Hz. #indicates P<0.05, Wilcoxon signed rank test. (d) Across 4–10 Hz stimulation frequencies, changes in spike-field coherence predicted changes in stability of functional connectivity for individual neurons (Spearmann rank order, n=320 neurons). (e) Comparison of CA1 spike-field coherence across a 30-min baseline period, 30 min of 7 Hz stimulation, and 2 h or post-stimulation recovery, in mice with CA1 transduction of ChR2 (blue) or GFP (black). (f) Over the 2 h following 7 Hz stimulation, CA1 neuronal functional connectivity in mice transduced with ChR2 showed an increase in stability relative to baseline. For (c,d), #indicates P<0.05, Wilcoxon signed rank test. For (c,e,f), all values indicate mean±s.e.m. (g) Neuronal functional connectivity strength also showed an increase in ChR2-transduced mice following 7 Hz stimulation. A similar change that was not seen in GFP-transduced mice. P value indicates results of Kolmogorov–Smirnov test.
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f8: Coherent firing induced by optogenetic stimulation of PV+ interneurons increases CA1 network stability and connection strength.(a) Perievent firing rasters (top) and perievent firing histograms (bottom) for a representative CA1 FS interneuron and three neighbouring principal neurons recorded from a Pvalb-IRES-CRE mouse expressing ChR2. Firing is shown over 250 s of recording before and during rhythmic (8 Hz) 473 nm light stimulation of PV+ interneurons. (b) A representative 5 s LFP trace (left) and perievent LFP raster (right) for one of the recording sites from a in baseline and stimulation conditions. (c) Changes in spike-field coherence (from baseline) induced by various frequencies of rhythmic PV+ interneuron stimulation in virally transduced neurons. Significant increases (from baseline) were present at stimulation frequencies between 4 and 10 Hz. #indicates P<0.05, Wilcoxon signed rank test. (d) Across 4–10 Hz stimulation frequencies, changes in spike-field coherence predicted changes in stability of functional connectivity for individual neurons (Spearmann rank order, n=320 neurons). (e) Comparison of CA1 spike-field coherence across a 30-min baseline period, 30 min of 7 Hz stimulation, and 2 h or post-stimulation recovery, in mice with CA1 transduction of ChR2 (blue) or GFP (black). (f) Over the 2 h following 7 Hz stimulation, CA1 neuronal functional connectivity in mice transduced with ChR2 showed an increase in stability relative to baseline. For (c,d), #indicates P<0.05, Wilcoxon signed rank test. For (c,e,f), all values indicate mean±s.e.m. (g) Neuronal functional connectivity strength also showed an increase in ChR2-transduced mice following 7 Hz stimulation. A similar change that was not seen in GFP-transduced mice. P value indicates results of Kolmogorov–Smirnov test.
Mentions: We next tested whether rhythmic PV+ interneuron activity is sufficient to augment CA1 oscillations and stabilize CA1 ensembles. To do this, we recorded network dynamics among CA1 neurons before, during, and after rhythmic optogenetic stimulation of PV+ interneurons in anaesthetized animals (Supplementary Fig. 12). In transgenic mice expressing Channelrhodopsin 2 (ChR2) in PV+ interneurons (PV:ChR2), stimulation across a range of frequencies led to rhythmic activation of FS interneurons, and rhythmic inhibition of neighbouring principal neurons (Supplementary Fig. 13a). Stimulation also led to frequency-specific, rhythmic activity in the CA1 LFP and enhanced neuronal spike-field coherence at the stimulation frequency (Supplementary Fig. 13a; Supplementary Fig. 15a). In contrast, stimulation above (18 Hz) or below (2 Hz) this range had relatively modest effects on spike-field coherence. Because PV-expressing interneurons outside CA1 can contribute to CA1 network oscillations32, we repeated these experiments in AAV-transduced Pvalb-IRES-CRE transgenic mice with CA1-targeted expression of ChR2. In these mice, rhythmic PV+ interneuron activation led to similar increases in CA1 rhythmic firing and LFP rhythmicity (Fig. 8a,b and Supplementary Fig. 14). This was true both under anaesthetized conditions (Fig. 8) and in awake, behaving mice (Supplementary Fig. 16). Again, the strongest effects on spike-field coherence were seen for stimulation frequencies between 4 and 10 Hz (Fig. 8c).

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