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Multi-site recordings in Tg4510 mice. Liam Scott. Hippocampus: Area. Area (mm2). 3m. 7m. 7 month male Tg4510 mice show decreased MWM performance and hippocampal cell loss. 3 vs. 7 month old Tg4510 male mice show:. (Wildtype for comparison). Data: Kawabe, Klein, Milici. - PowerPoint PPT Presentation
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Multi-site recordings in Tg4510 mice
Liam Scott
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
7 month male Tg4510 mice show decreased MWM performance and hippocampal cell loss
Are
a (
mm
2)
1
1.2
1.4
1.6
1.8
2
2.2
2.4
2.6
2.8
3 months 6 months 8 months 10 months
Wild Type
Bigenic 4510
40
50
60
70
80
90
100
110
% W
ild T
ype
3 M 6M 8 M 10 M
Wild Type
Bigenic 4510
Normalized Ca1 Thickness
Hippocampus: Area
1 2 3 40
500
1000
1500
M++M--
F++F--
Day of testing
Len
gth
of
Pat
h (
cm)
***
*
3m
1 2 3 40
500
1000
1500
** * ** *
**
Day of testing
7m
3 vs. 7 month old Tg4510 male mice show:
(Wildtype for comparison)
Data: Yabe, Moore, Roof Data: Kawabe, Klein, Milici
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
1174 1176 1178 1180 1182 1184 1186 1188 1190 1192 1194 1196 1198 1200 1202 1204 1206 1208 1210 1212s
Keyboard311000
0
-1000
uV
CA
1 E
EG
1
5274 5276 5278 5280 5282 5284 5286 5288 5290 5292 5294 5296 5298 5300 5302 5304 5306 5308 5310 5312s
Keyboard311000
0
-1000
uVC
A1
EEG
1
Stimulation of the nPO drives the hippocampal EEG in anesthetized rats and mice
NPO
Hippo
EEG Stimulus
6-seconds
0.06 0.08 0.10 0.12 0.14 0.16
5.5
6.0
6.5
7.0
7.5
8.0
Fre
quen
cy (
Hz)
Stim Current (mA)
Theta Frequency
0.06 0.08 0.10 0.12 0.14 0.1615.0k20.0k
25.0k30.0k
35.0k40.0k
45.0k50.0k
Theta Power
The
ta P
ower
(V
2 )
Stim Current (mA)
0 5 10 15HzFrequency
10000
5000
0
uV^2
CA
1 E
EG
1
0 5 10 15HzFrequency
2000
1000
0
uV^2
CA
1 E
EG
1
–5-HT
–Hippocampal Formation
–pcells
–Median Raphe
–Gl
u
–ga
ba
–ACh
–Medial Septum
–Nucleus Pontis Oralis
–(nPO)
–Gl
u
–Supramammilary Bodies
–(SUM)
–Gl
u
–ga
ba
–ga
ba –ga
ba
–ga
ba
–5-HT
–Adapted from: RP Vertes (2005) Hippocampus 15:923-35
–= +–= -
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
Determining electrode position using stimulation of nPO
4
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
7 month male Tg4510 mice show decreased nPO-evoked hippocampal theta power and total power
Peak Frequency Relative Theta Power
Theta Power Total Power
** *
*
*
* * * *
***
**
*
*
**
* *
* *
**
(*=P<0.05, **=P<0.01, ***=P<0.001 ; unpaired t-test)
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
Perforant path – dentate gyrus LTP
6
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
Determining electrode position using stimulation of perforant path
7
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
7 month male Tg4510 mice show reduced amplitude of perforant path-evoked dentate gyrus population spike
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
7 month male Tg4510 mice show reduced amplitude of perforant path-evoked dentate gyrus population spike
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
7 month male Tg4510 mice show no change in perforant path - dentate gyrus LTP
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
–control
CA-1
DG
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
CA-1
DG
DG population spike
CA1 population spike
–Tg
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements.
Summary
Stimulated theta• No change in theta frequency or relative theta• Reduction in theta power and total power
PP-DG LTP• Reduction in amplitude of evoked population spike• No change in LTP due to HFS
All observations can be explained by reduction in cell number in hippocampal formation???
14
Confidential and Internal to Pfizer - subject to works council and/or union consultations and other legal requirements. 15
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