University of Alberta

Year: 2000

Evidence for spatial modules mediated by temporal synchronization of carbachol-induced gamma rhythm in medial entorhinal cortex

PMID: 11027250

Dickson CT, Biella G, de Curtis M

J. Neurosci. 2000 Oct;20(20):7846-54


Fast (gamma) oscillations in the cortex underlie the rapid temporal coordination of large-scale neuronal assemblies in the processing of sensory stimuli. Cortical gamma rhythm is modulated in vivo by cholinergic innervation from the basal forebrain and can be generated in vitro after exogenous cholinergic stimulation. Using the isolated guinea pig brain, an in vitro preparation that allows for the study of an intact cerebrum, we studied the spatial features of gamma activity evoked by the cholinomimetic carbachol (CCh) in the medial entorhinal cortex (mEC). gamma activity induced by either arterial perfusion or intraparenchymal application of CCh showed a phase reversal across mEC layer II and was reduced or abolished in a spatially localized region by focal infusions of atropine, bicuculline, and CNQX. In addition, a spatially restricted zone of gamma activity could be induced by passive diffusion of CCh from a recording pipette. Finally, gamma oscillations recorded at multiple sites across the surface of the mEC using array electrodes during arterial perfusion of CCh demonstrated a decline in synchronization (coherence) as the interelectrode distance increased. This effect was independent of the signal amplitude and was specific for gamma as opposed to theta-like activity induced by CCh in the same experiments. These results suggest that CCh-induced gamma oscillations in the mEC are mediated through direct muscarinic excitation of a highly localized reciprocal inhibitory-excitatory network located in superficial layers. We propose that functional cortical modules of highly synchronous gamma oscillations may organize incoming (cortical) and outgoing (hippocampal) information in the mEC.

Oscillatory activity in entorhinal neurons and circuits. Mechanisms and function

PMID: 10911871

Dickson CT, Magistretti J, Shalinsky M, Hamam B, Alonso A

Ann. N. Y. Acad. Sci. 2000 Jun;911:127-50


Layers II and V of the entorhinal cortex (EC) occupy a privileged anatomical position in the temporal lobe memory system that allows them to gate the main flow of information in and out of the hippocampus, respectively. In vivo studies have shown that layer II of the EC is a robust generator of theta as well as gamma activity. Theta may also be present in layer V, but the layer V network is particularly prone to genesis of short-lasting high-frequency oscillations (“ripples”). Interestingly, in vitro studies have shown that EC layers II and V, but not layer III, have the potential to act as independent pacemakers of population oscillatory activity. Moreover, it has also been shown that subgroups of principal neurons both within layers II and V, but not layer III, are endowed with autorhythmic properties. These are characterized by subthreshold oscillations where the depolarizing phase is driven by the activation of “persistent” Na+ channels. We propose that the oscillatory properties of layer II and V neurons and local circuits are responsible for setting up the proper temporal dynamics for the coordination of the multiple sensory inputs that converge onto EC and thus help to generate sensory representations and memory encoding.

Properties and role of I(h) in the pacing of subthreshold oscillations in entorhinal cortex layer II neurons

PMID: 10805658

Dickson CT, Magistretti J, Shalinsky MH, Fransén E, Hasselmo ME, Alonso A

J. Neurophysiol. 2000 May;83(5):2562-79


Various subsets of brain neurons express a hyperpolarization-activated inward current (I(h)) that has been shown to be instrumental in pacing oscillatory activity at both a single-cell and a network level. A characteristic feature of the stellate cells (SCs) of entorhinal cortex (EC) layer II, those neurons giving rise to the main component of the perforant path input to the hippocampal formation, is their ability to generate persistent, Na(+)-dependent rhythmic subthreshold membrane potential oscillations, which are thought to be instrumental in implementing theta rhythmicity in the entorhinal-hippocampal network. The SCs also display a robust time-dependent inward rectification in the hyperpolarizing direction that may contribute to the generation of these oscillations. We performed whole cell recordings of SCs in in vitro slices to investigate the specific biophysical and pharmacological properties of the current underlying this inward rectification and to clarify its potential role in the genesis of the subthreshold oscillations. In voltage-clamp conditions, hyperpolarizing voltage steps evoked a slow, noninactivating inward current, which also deactivated slowly on depolarization. This current was identified as I(h) because it was resistant to extracellular Ba(2+), sensitive to Cs(+), completely and selectively abolished by ZD7288, and carried by both Na(+) and K(+) ions. I(h) in the SCs had an activation threshold and reversal potential at approximately -45 and -20 mV, respectively. Its half-activation voltage was -77 mV. Importantly, bath perfusion with ZD7288, but not Ba(2+), gradually and completely abolished the subthreshold oscillations, thus directly implicating I(h) in their generation. Using experimentally derived biophysical parameters for I(h) and the low-threshold persistent Na(+) current (I(NaP)) present in the SCs, a simplified model of these neurons was constructed and their subthreshold electroresponsiveness simulated. This indicated that the interplay between I(NaP) and I(h) can sustain persistent subthreshold oscillations in SCs. I(NaP) and I(h) operate in a “push-pull” fashion where the delay in the activation/deactivation of I(h) gives rise to the oscillatory process.

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