Development of Cholinergic Modulation and Graded Persistent Activity in Layer V of Medial Entorhinal Cortex

Abstract

During muscarinic modulation, principal neurons from layer V of rat medial entorhinal cortex (mEC) respond to repeated applications of a brief stimulus with a graded change in persistent firing frequency. This pattern of discharge has been proposed to represent an intrinsic mechanism for short-term memory operations. To investigate the implementation of persistent activity in mEC during development, we characterized the electrophysiological properties of layer V principal neurons in the mEC over a range of postnatal stages. We observed significant differences in both passive (resistance, time constant, and resting membrane potential) and active properties (threshold, action potential, and adaptation) of principal neurons from rats aged 5-7, 10-13, 16-19, and 21-23 days. We also examined the properties of muscarinic-dependent persistent activity in EC slices from different age groups. Recordings were conducted using the perforated-patch whole cell technique because persistent activity runs down in the ruptured-patch configuration. Although no neuron in the youngest group exhibited graded persistent activity in response to muscarinic receptor activation, this activity was recorded in the 10- to 13-day-old group and its occurrence increased from 69% in the 16- to 19-day-old group to 76% in the 21- to 23-day-old group. This postnatal increase in neurons endowed with persistent firing properties in mEC was found to parallel the increase in density of ChAT-positive immunostaining of fibers and the developmental changes in M1 muscarinic receptor mRNA levels. All these data suggest that the implementation of mnemonic properties in mEC principal neurons matches the ontogenic development of afferent cholinergic circuits and their signaling components.

Cellular properties of principal neurons in the rat entorhinal cortex. II. The medial entorhinal cortex

“…These observations are in contrast to two reports that showed that at least two-third of principal neurons in MEC LV have oscillations with a frequency ranging from 3 to 30 Hz (Schmitz et al, 1998) or 3.4 to 14.8 Hz (Hamam et al, 2000). Although we cannot exclude that differences with respect to the recording electrode used (sharp electrode versus whole cell patch pipette) contributed to the observed differences, these differences likely reflect age-related changes (Reboreda et al, 2007). It is thus likely that the network integration in LV of younger animals is less frequency dependent than in older animals (Hutcheon et al, 1996;Hamam et al, 2002;Hafting et al, 2008).…”

TRPC channels underlie cholinergic plateau potentials and persistent activity in entorhinal cortex

“…Because of the complexity of heteromerization among subunits within the TRPC family, a combination of multiple approaches including molecular biology is needed for the molecular identification of the channels that mediate persistent firing in mEC. The firing frequency during persistent activity can be up-or down-graded in mEC in specific conditions (Egorov et al, 2002;Reboreda et al, 2007;Tahvildari et al, 2008). The role of TRPC channels in graded activity will remain to be investigated.…”

“…Layer V principal neurons of medial entorhinal cortex (mEC) display activity-dependent plateau potentials and nonsynaptic intrinsic persistent firing evoked by muscarinic receptor activation (Egorov et al, 2002;Reboreda et al, 2007). Persistent firing has been associated with the delay phase in delayed match or nonmatch to sample memory trials (Suzuki et al, 1997;Young et al, 1997).…”

Spontaneous Bursting Activity in the Developing Entorhinal Cortex

“…In mature mEC neurons, I CAN underlies persistent firing (Klink and Alonso, 1997;Egorov et al, 2002;AlYahya et al, 2003;Fransén et al, 2006). However, I CAN -mediated persistent activity requires activation of muscarinic-cholinergic receptors or mGluRs, and the postnatal increase in neurons endowed with persistent firing properties in mEC was found to parallel the development of the cholinergic system (Reboreda et al, 2007). Thus, the decrease of I CAN might result from its functional switch from spontaneous Ca 2ϩ -dependent activation at an early developmental stage to a muscarinic receptor/ mGluR-mediated activation at a mature stage.…”