Abstract

Hippocampal place cells that are activated sequentially
during active waking get reactivated in a temporally compressed (5–20
times) manner during slow-wave-sleep and quiet waking. The two-stage
model of the hippocampus suggests that neural activity during awaking
supports encoding function while temporally compressed reactivation
(replay) supports consolidation. However, the mechanisms supporting
different neural activity with different temporal scales during encoding
and consolidation remain unclear. Based on the idea that acetylcholine
modulates functional transition between encoding and consolidation,
we tested whether the cholinergic modulation may adjust intrinsic network
dynamics to support different temporal scales for these two modes
of operation. Simulations demonstrate that cholinergic modulation of
the calcium activated non-specific cationic (CAN) current and the synaptic
transmission may be sufficient to switch the network dynamics
between encoding and consolidation modes. When the CAN current is
active and the synaptic transmission is suppressed, mimicking the high
acetylcholine condition during active waking, a slow propagation of
multiple spikes is evident. This activity resembles the firing pattern of
place cells and time cells during active waking. On the other hand,
when CAN current is suppressed and the synaptic transmission is intact,
mimicking the low acetylcholine condition during slow-wave-sleep, a
time compressed fast (~10 times) activity propagation of the same set
of cells is evident. This activity resembles the time compressed firing
pattern of place cells during replay and pre-play, achieving a temporal
compression factor in the range observed in vivo (5–
20 times). These observations suggest that cholinergic
system could adjust intrinsic network dynamics suitable
for encoding and consolidation through the modulation
of the CAN current and synaptic conductance
in the hippocampus.