mGluR‐dependent persistent firing in entorhinal cortex layer III neurons

Abstract

Persistent firing is believed to be a crucial mechanism for memory function including working memory. Recent in vivo and in vitro findings suggest an involvement of metabotropic glutamate receptors (mGluRs) in persistent firing. Using whole-cell patch recording techniques in a rat entorhinal cortex (EC) slice preparation, we tested if EC layer III neurons display persistent firing due to mGluR-activation, independently from cholinergic activation. Stimulation of the angular bundle drove persistent firing in 90% of the cells in the absence of cholinergic agonist. The persistent firing was typically stable for more than 4.5 min at which point persistent firing was terminated by the experimenter. The average frequency of the persistent firing was 2.1 Hz, ranging from 0.4 to 5.5 Hz. This persistent firing was observed even in the presence of atropine (2 μM), suggesting that the persistent firing can occur independent of cholinergic activation. Furthermore, ionotropic glutamate and GABAergic synaptic blockers (2 mM kynurenic acid, 100 μM picrotoxin and 1 μM CGP55845) did not block the persistent firing. On the other hand, blockers of group I mGluRs (100 μM LY367385 and 20 μM MPEP) completely blocked or suppressed the persistent firing. An agonist of group I mGluRs (20 μM DHPG) greatly enhanced the persistent firing induced by current injection. These results indicate that persistent firing can be driven through group I mGluRs in entorhinal layer III neurons suggesting that glutamatergic synaptic input alone could enable post-synaptic neurons to hold input signals in the form of persistent firing.

Functional Dissociation within the Entorhinal Cortex for Memory Retrieval of an Association between Temporally Discontiguous Stimuli

“…These differences in anatomical connectivity between the LEC and MEC may explain the observed functional dissociation in the trace paradigm, whereby the LEC may function to maintain CS information during the trace interval by sustained neuronal activity, enabling hippocampal or prefrontal networks to recover patterns of neuronal activities selective for the previously acquired association (McEchron and Disterhoft, 1997;Takehara-Nishiuchi and McNaughton, 2008). Targeted manipulations to self-sustaining entorhinal activity using a muscarinic or metabotropic glutamate receptor antagonist (Klink and Alonso, 1997;Yoshida et al, 2008;Esclassan et al, 2009) could test this possibility.…”

A Cholinergic-Dependent Role for the Entorhinal Cortex in Trace Fear Conditioning

“…A fraction of cortical cholinergic interneurons that express vasoactive intestinal polypeptide has been suggested to participate in local cerebrovascular regulation (Chédotal et al, 1994), but their functional role, in general, and in the EC, in particular, is largely unknown (Bayraktar et al, 1997) and may have been underestimated. Alternatively, we cannot exclude that the cholinergic deafferentation may have induced compensatory changes in the expression of metabotropic glutamate receptors, resulting in facilitation or restoration of persistent firing in entorhinal cortex neurons (Yoshida et al, 2008).…”

Spontaneous Bursting Activity in the Developing Entorhinal Cortex

“…8 B; also supplemental Table 4, available at www.jneurosci.org as supplemental material). We also tested neurons in the presence of the group I and II metabotropic glutamate receptor (mGluR) antagonist E4CPG to exclude a possible early mGluR-dependent firing (Yoshida et al, 2008). Bath application of the E4CPG (200 M) did not abolish the prolonged intrinsic bursting activity of immature mEC LIII neurons (n ϭ 4).…”