NMDA recep
tors (NMDARs) play an impor
tan
t role in neural plas
tici
ty including long-
term po
ten
tia
tion and long-
term depression, which are likely
to explain
their impor
tance for learning and memory. Cogni
tive decline is a major problem facing an ageing human popula
tion, so much so
tha
t i
ts reversal has become an impor
tan
t goal for scien
tific research and pharmaceu
tical developmen
t. Enhancemen
t of NMDAR func
tion is a core s
tra
tegy
toward
this goal. In
this review we indica
te some of
the major ways of po
ten
tia
ting NMDAR func
tion by bo
th direc
t and indirec
t modula
tion. There is good evidence
tha
t bo
th posi
tive and nega
tive modula
tion can enhance func
tion sugges
ting
tha
t a sub
tle approach correc
ting imbalances in par
ticular clinical si
tua
tions will be required. Excessive ac
tiva
tion and
the resul
tan
t dele
terious effec
ts will need
to be carefully avoided. Finally we describe some novel posi
tive allos
teric modula
tors of NMDARs, wi
th some subuni
t selec
tivi
ty, and show ini
tial evidence of
their abili
ty
to affec
t NMDAR media
ted even
ts.
This article is part of a Special Issue entitled ¡®Cognitive Enhancers¡¯.