Title:
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Preferred theta-phase of firing in rat hippocampal place cells : effects of novelty and scopolamine
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The hippocampus supports novelty detection and memory, functions linked to each other and to
the theta rhythm. We examined the theta phase preference of CA1 place cells firing. Novelty may
favour an encoding mode by enhancing synaptic plasticity and extrinsic sensory inputs (entorhinal
cortex to CAn while familiarity may favour a retrieval mode by reducing/altering plasticity and
enhancing intrinsic inputs (CA3 to CA1). Entorhinal and CA3 inputs arrive in CA1 at different theta
phases. Novelty elicits a later preferred phase of CA1 place cell firing, supporting the idea of a
novelty-elicited switch prioritising the encoding of novel sensory cues.
Mechanisms underlying changes in preferred theta phase were explored by testing the effect of
systemic scopolamine (a muscarinic cholinergic antagonist known to impair learning) in familiar
and novel environments. CA1 place cells and EEG activity was recorded from foraging rats in two
sessions in a familiar environment with interleaved novelty exposure. A different novel
environment was used in each session. Saline vehicle or scopolamine (0.4 mg/kg, Lp.) was injected
before exposure to the novel environment. A third, similar phase of the experiment tested the
effect of scopolamine in the familiar environment.
The results showed that 1) the preferred theta phase was later in the novel environment under
saline, replicating Lever et al. (2010); 2) Scopolamine elicited an earlier preferred theta phase in
the familiar environment; 3) Scopolamine strongly disrupted the novelty-elicited phase
preference, with preferred phase (relative to baseline) being more varied across rats.
These results support a relationship between novelty, theta phase, and synaptic plasticity
mediated by cholinergic signalling: the later preferred phase in novelty would coincide with the
peak of theta, where LTP induction is maximal. Promotion and impairment of CA1 encoding under,
respectively, novelty and scopolamine may involve a mechanism that shifts the preferred theta
phase of firing.
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