Preferred theta-phase of firing in rat hippocampal place cells : effects of novelty and scopolamine

• Main Author: Douchamps, Vincent
• Published: University of Leeds 2011
• Subjects: 616.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.659031

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.