Table 2a.
Cell-type specific manipulations in the hippocampus in object exploration tests. AAV: adeno-associated virus or recombinant adeno-associated virus; CCK: cholecystokinin; C.N.E.: compatible with no important effect; CNO: clozapine-N-oxide; DG: dentate gyrus; dHPC: dorsal hippocampus; DTA: diphtheria toxin subunit A; h: hours; ITI: inter-trial interval; min: minutes; OLM: oriens lacunosum moleculare; OVX: ovariectomy; PV: parvalbumin; s: seconds; SALB: salvinorin B; TeLC: tetanus toxin light chain; vHPC: ventral hippocampus; (+) excitation; (−) inhibition. *The control animals also showed the deficits. **Decreased exploration of the old object.
| Animal | Treatment | Time of activation | Encoding | ITI | Findings | Reference |
|---|---|---|---|---|---|---|
| NOP test: | ||||||
| Chrna2-Cre male mice |
Ablation of vHPC OLM interneurons AAV9-FLEX-DTA into vHPC |
Not required | 10 min | 20 min | C.N.E. | Haam et al., 2018 |
| Amigo2-Cre male mice |
(−) CA2 excitatory neurons AAV5-EF1α-FLEX-TeLC into CA2 |
Not required | 5 min 5 min x4 |
1 h 1 h |
C.N.E. | Hitti & Siegelbaum, 2014 |
| BAC CRH-Cre mice both sexes |
Ablation of dHPC CRH neurons AAV-FLEX-DTA into dHPC |
Not required | 5 minx3 | 3 h 24 h |
Impaired C.N.E. |
Hooper et al., 2018 |
| PV-Cre male mice |
(+) vHPC PV neurons AAV-EF1a-DIO-hM3Dq into vHPC |
Pre-sample CNO 1.0 mg/kg, i.p. |
10 min | 30 min | C.N.E. | Wang et al., 2018 |
| CaMKII2α-Cre male mice |
(−) vHPC excitatory neurons AAV-EF1a-DIO-hM4Di into vHPC |
Pre-sample CNO 1.0 mg/kg, i.p. |
10 min | 30 min | C.N.E. | Wang et al., 2018 |
| BAC CRH-Cre mice both sexes |
(−) dHPC CRH neurons AAV8-hSyn-DIO-hM4Di into dHPC |
Pre-sample CNO 10 mg/kg, i.p. |
5 minx3 | 3 h 24 h |
Impaired* C.N.E. |
Hooper et al., 2018 |
| PV-Cre male mice |
(+) dDG PV neurons Lenti-EF1a-DIO-hM3Dq into dDG |
Pre-sample CNO 0.5 mg/kg, .i.p. |
10min 10min |
1h 24h |
C.N.E. C.N.E. |
Zou et al., 2016 |
| C57BL/6J male mice |
(+) dHPC neurons AAV2/8-hSyn-hM3Dq into dHPC |
Pre-sample CNO 3 mg/kg, i.p. |
3 min | 24h | C.N.E. | Lopez et al., 2016 |
| C57BL/6J male mice |
(+) dHPC excitatory neurons AAV2/8-CaMKIIα-hM3Dq into dHPC |
Pre-sample CNO 3 mg/kg, i.p. |
3 min | 24h | C.N.E. | Lopez et al., 2016 |
| C57BL/6J male mice |
(−) dHPC neurons AAV2/8-hSyn-hM4Di into dHPC |
Pre-sample CNO 3 mg/kg, i.p. |
10 min | 24h | C.N.E. | Lopez et al., 2016 |
| C57BL/6J male mice |
(−) dHPC excitatory neurons AAV2/8-CaMKIIα-hM4Di into dHPC |
Pre-sample CNO 3 mg/kg, i.p. |
10 min | 24h | C.N.E. | Lopez et al., 2016 |
| C57BL/6 | (−) dHPC excitatory neurons female OVX mice |
Pre-sample AAV8-CaMKIIα-hM4Di into dHPC |
reach 30s CNO 2 mg/kg, i.p. |
24 h | C.N.E. | Tuscher et al., 2018 |
| Chrna2-Cre mice both sexes |
(+) intermediate CA1 OLMα2 neurons AAV-EF1a-DIO-ChR2 into intermediate HPC |
During the sample trial 8 Hz only on one obj. |
10 min | 1 h 24 h |
Impaired Impaired |
Siwani et al., 2018 |
| Chrna2-Cre mice both sexes |
(+) intermediate CA1 OLMα2 neurons AAV-EF1a-DIO-ChR2 into intermediate HPC |
During the sample trial 8 Hz if not exploring obj. |
10 min | 1 h | C.N.E. | Siwani et al., 2018 |
| Chrna2-Cre mice both sexes |
(−) dorsal HPC OLMα2 neurons AAV9-FLEX-Arch into dorsal HPC |
During the sample trial 8 Hz only on one obj. |
10 min | 1 h | C.N.E. | Siwani et al., 2018 |
| Chrna2-Cre mice both sexes |
(−) intermediate CA1 OLMα2 neurons AAV9-FLEX-Arch into intermediate HPC |
During the sample trial 8Hz only on one obj. |
10 min | 1 h | Facilitated** | Siwani et al., 2018 |
| GAD65-Cre male mice |
(+) dHPC GABAergic neurons AAV2-CAG-DIO-hM3Dq into dHPC |
Post-sample CNO 0.5 mg/kg, i.p. |
10 min | 24 h | C.N.E. | Yu et al., 2018 |
| Chrna2-Cre mice both sexes |
(+) intermediate CA1 OLMα2 neurons AAV-EF1a-DIO-ChR2 into intermediate HPC |
Post-sample 8 Hz for 10 min |
10 min | 24 h | C.N.E. | Siwani et al., 2018 |
| C57BL/6 female OVX mice |
(−) dHPC excitatory neurons AAV8-CaMKIIα-hM4Di into dHPC |
Post-sample CNO 2-8 mg/kg, i.p. |
reach 30s | 24 h | C.N.E. | Tuscher et al., 2018 |
| C57BL/6 female OVX mice |
(−) dHPC excitatory neurons AAV8-CaMKIIα-KORD into dHPC |
Post-sample SALB 10 mg/kg, i.p. |
reach 30s | 24 h | Impaired | Tuscher et al., 2018 |
| POMC-Cre mice both sexes |
(+) dDG granule neurons AAV5-hSyn-DIO-hM3Dq into dDG |
Pre-test CNO 0.3 mg/kg, i.p. |
15 min | 24 h | C.N.E. | Kahn et al., 2019 |
| C57BL/6 male mice |
(−) vHPC excitatory neurons AAV-CaMKII-NpHR3.0 into vHPC |
During test trial constant light |
4 min | 10 min | C.N.E. | Sun et al., 2020 |
| Chrna2-Cre mice both sexes |
(+) intermediate CA1 OLMα2 neurons AAV-EF1a-DIO-ChR2 into intermediate HPC |
During the sample + test 8 Hz only on one obj. |
10 min | 1 h | C.N.E. | Siwani et al., 2018 |
| Dlx5/6-Flp: nNOS-Cre both sexes |
(+) HPC nNOS long-projecting neurons AAV-DJ-Con/Fon-ChR2 into dHPC |
During sample + test 7 Hz |
10 min | 24 h | C.N.E. | Wick et al., 2019 |
| PV-Cre: ChR2 both sexes |
(+) dHPC PV neurons Opto-fiber in dHPC |
During sample + test 7 Hz |
10 min | 24 h | C.N.E. | Zeidler et al., 2020 |
| NLP test: | ||||||
| Chrna2-Cre male mice |
Ablation of vHPC OLM interneurons AAV-FLEX-DTA into vHPC |
Not required | 10 min | 20 min | Impaired | Haam et al., 2018 |
| PV-Cre male mice |
(+) vHPC PV neurons AAV-EF1a-DIO-hM3Dq into vHPC |
Pre-sample CNO 1.0 mg/kg, i.p. |
10 min | 30 min | C.N.E. | Wang et al., 2018 |
| CaMKII2α-Cre male mice |
(−) vHPC excitatory neurons AAV-EF1a-DIO-hM4Di into vHPC |
Pre-sample CNO 1.0 mg/kg, i.p. |
10 min | 30 min | Impaired | Wang et al., 2018 |
| C57BL/6 female OVX mice |
(−) dHPC excitatory neurons AAV8-CaMKIIα-hM4Di into dHPC |
Pre-sample CNO 2 mg/kg, i.p. |
reach 30s | 4 h | Impaired | Tuscher et al., 2018 |
| C57BL/6J male mice |
(+) dHPC neurons AAV2/8-hSyn-hM3Dq into dHPC |
Pre-sample CNO 3 mg/kg, i.p. |
3 min | 24h | Facilitated | Lopez et al., 2016 |
| C57BL/6J male mice |
(+) dHPC excitatory neurons AAV2/8-CaMKIIα-hM3Dq into dHPC |
Pre-sample CNO 3 mg/kg, i.p. |
3 min | 24h | Facilitated | Lopez et al., 2016 |
| C57BL/6J male mice |
(−) dHPC neurons AAV2/8-hSyn-hM4Di into dHPC |
Pre-sample CNO 3 mg/kg, i.p. |
10 min | 24h | Impaired | Lopez et al., 2016 |
| C57BL/6J male mice |
(−) dHPC excitatory neurons AAV2/8-CaMKIIα-hM4Di into dHPC |
Pre-sample CNO 3 mg/kg, i.p. |
10 min | 24h | Impaired | Lopez et al., 2016 |
| Emx1-Cre: AlstR mice |
(−) dHPC excitatory neurons cannulae into dHPC |
Pre-sample allatostatin 1 μM/0.5 μl |
10 min | 24 h | Impaired | Haettig et al., 2013 |
| Dlx5/6-Cre: AlstR mice |
(−) dHPC GABAergic neurons cannulae into dHPC |
Pre-sample allatostatin 1 μM/0.5 μl |
10 min | 24 h | Impaired | Haettig et al., 2013 |
| C57BL/6 female OVX mice |
(−) dHPC excitatory neurons AAV8-CaMKIIα-hM4Di into dHPC |
Post-sample CNO 2 mg/kg, i.p. |
reach 30s | 4 h | Impaired | Tuscher et al., 2018 |
| C57BL/6 female OVX mice |
(−) dHPC excitatory neurons AAV8-CaMKIIα-KORD into dHPC |
Post-sample SALB 10 mg/kg, i.p. |
reach 30s | 4 h | Impaired | Tuscher et al., 2018 |
| GAD65-Cre male mice |
(+) dHPC GABAergic neurons AAV2-CAG-DIO-hM3Dq into dHPC |
Post-sample CNO 0.5 mg/kg, i.p. |
10 min | 24 h | Impaired | Yu et al., 2018 |
| C57BL/6N male mice |
(−) dHPC GABAergic neurons AAV2-VGAT-Cre + AAV2-EF1a-DIO-hM4Di |
Post-sample CNO 0.5 mg/kg, i.p. |
10 min | 24 h | Impaired | Yu et al., 2018 |
| Dlx5/6-Flp: nNOS-Cre both sexes |
(+) HPC nNOS long-projecting neurons AAV-DJ-Con/Fon-ChR2 into dHPC |
During sample + test 7 Hz |
10 min | 24 h | Impaired | Wick et al., 2019 |
| PV-Cre: ChR2 both sexes |
(+) HPC PV neurons Opto-fiber in HPC |
During sample + test 7 Hz |
5 min | 24 h | C.N.E. | Zeidler et al., 2020 |
| NLP test (3 objects): | ||||||
| C57BL/6 mice both sexes |
(+) dDG excitatory neurons AAV5-CaMKIIα-hM3Dq into dDG |
Pre-test CNO 0.3 mg/kg, i.p. |
6 min x3 | 24 h | Impaired | Kahn et al., 2019 |
| C57BL/6 mice both sexes | (−) dDG excitatory neurons AAV5-CaMKIIα-hM4Di into dDG |
Pre-test CNO 1.5 mg/kg, i.p. |
6 min x3 | 24 h | Impaired | Kahn et al., 2019 |
| POMC-Cre mice both sexes |
(+) dDG granule neurons AAV5-hSyn-DIO-hM3Dq into dDG |
Pre-test CNO 0.3 mg/kg, i.p. |
6 min x3 | 24 h | Impaired | Kahn et al., 2019 |
| C57BL/6 or wildtype both sexes mice |
(−) dHPC excitatory neurons AAV5-CaMKIIα-hM4Di into dHPC |
Pre-sample + Pre-test CNO 1.0 mg/kg, i.p. |
6 min x3 | 24 h | Impaired | Kahn et al., 2020 |
| C57BL or wildtype both sexes mice |
(−) vHPC excitatory neurons AAV5-CaMKIIα-KORD into vHPC |
Pre-sample + Pre-test SALB 1.0 mg/kg, s.c. |
6 min x3 | 24 h | C.N.E. | Kahn et al., 2020 |