University of Alberta

Month: January 2008

Differential induction of long-term potentiation in the horizontal versus columnar superficial connections to layer II cells of the entorhinal cortex

PMID: 18604300

Ma L, Alonso A, Dickson CT

Neural Plast. 2008;2008:814815


The entorhinal cortex (EC) is a nodal and independent mnemonic element of the medial temporal lobe memory circuit as it forms a bidirectional interface between the neocortex and hippocampus. Within the EC, intra- and inter-lamellar associational connections occur via horizontal and columnar projections, respectively. We undertook a comparative study of these two inputs as they converge upon EC layer II cells using whole-cell patch techniques in an adult rat EC horizontal slice preparation in which the deepest layers (V-VI) had been dissected out. Electrical stimulation of layers I and III during GABA blockade allowed us to study excitatory synaptic properties and plasticity in the horizontal and columnar fibre systems, respectively. Both pathways exhibited AMPA- and NMDA-receptor mediated transmission and both exhibited long-term potentiation (LTP) after high-frequency (tetanic) stimulation. LTP in the horizontal, but not in the columnar pathway, was blocked by NMDA receptor antagonism. Intriguingly, LTP in both appeared to be mediated by post synaptic increases in Ca2+ that may be coupled to differing second messenger pathways. Thus, the superficial excitatory horizontal and columnar associative pathways to layer II have divergent mechanisms for LTP which may endow the EC with even more complex and dynamic processing characteristics than previously thought.

Cyclic and sleep-like spontaneous alternations of brain state under urethane anaesthesia

PMID: 18414674

Clement EA, Richard A, Thwaites M, Ailon J, Peters S, Dickson CT

PLoS ONE 2008;3(4):e2004


BACKGROUND: Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state.

METHODOLOGY/PRINCIPAL FINDINGS: Long-duration, multi-site forebrain field recordings were performed in urethane-anaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame ( approximately 11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane.

CONCLUSIONS/SIGNIFICANCE: Our results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep. The use of urethane anaesthesia as a model system will facilitate mechanistic studies into sleep-like brain states and their alternations. In addition, it could also be exploited as a tool for the discovery of new molecular targets that are designed to promote sleep without compromising state alternations.

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