One approach
to
trea
tmen
t of nega
tive cogni
tive effec
ts associa
ted wi
th Alzheimer's disease and schizophrenia may involve ac
tiva
tion of neuronal
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tle="greek small le
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tinic ace
tylcholine recep
tors (nAChRs). We used
the
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tle="greek small le
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tive par
tial agonis
t 3-(4-hydroxy, 2-me
thoxy-benzylidene)anabaseine (4OH-GTS-21),
the
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tor 5-hydroxyindole (5-HI), and recombinan
t adeno-associa
ted virus (rAAV)-media
ted
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tle="greek small le
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transfer in order
to
tes
t the hypo
thesis whe
ther combining
these s
tra
tegies would significan
tly increase indirec
t measures of
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tle="greek small le
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tion, including measures of spon
taneous synap
tic even
ts in CA1 pyramidal cells. 5-HI (1 mM), and 5-HI (1 mM) + 4OH-GTS-21 (5 μM) increased
the frequency of APV- and NBQX-sensi
tive curren
ts, while 5-HI + 4OH-GTS-21 increased
the frequency and ampli
tude of bicuculline-sensi
tive curren
ts. Effec
ts on EPSCs were blocked wi
th
te
trodo
toxin (TTX) (1 μM), bu
t no
t by me
thyllycaconi
tine (MLA) (50 nM). Nei
ther TTX nor MLA reduced
the po
ten
tia
tion of IPSC frequencies. However, TTX blocked, and in some cases MLA reduced,
the po
ten
tia
tion of IPSC ampli
tudes. These da
ta sugges
t tha
t effec
ts of 5-HI + 4OH-GTS-21 on EPSC frequency were associa
ted wi
th ac
tion po
ten
tial-dependen
t transmi
tter release produced by 5HI, and
tha
t po
ten
tia
tion of IPSC ampli
tudes resul
ted a
t leas
t in par
t, from ac
tiva
tion of
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tle="greek small le
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ted
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transfer did no
t al
ter
the magni
tude of effec
ts produced by 5-HI or 5-HI + 4OH-GTS-21. Thus, al
though we previously showed
tha
t direc
t measures of
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tle="greek small le
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tion were enhanced by
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ti
tle="greek small le
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transfer, indirec
t measures of
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ties/204e.gif" al
t="greek small le
tter alpha"
ti
tle="greek small le
tter alpha" border="0">7 nAChRs func
tion were no
t significan
tly enhanced by combining
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t="greek small le
tter alpha"
ti
tle="greek small le
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transfer wi
th ei
ther agonis
t ac
tiva
tion or posi
tive allos
teric modula
tion of
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