Development of Theta Rhythmicity in Entorhinal Stellate Cells of the Juvenile Rat

Abstract

. Mature stellate cells of the rat medial entorhinal cortex (EC), layer II, exhibit subthreshold membrane potential oscillations (MPOs) at theta frequencies (4 -12 Hz) in vitro. We find that MPOs appear between postnatal days 14 (P14) and 18 (P18) but show little further change by day 28ϩ (P28 -P32). To identify the factors responsible, we examined the electrical responses of developing stellate cells, paying attention to two currents thought necessary for mature oscillation: the h current I h , which provides the slow rectification required for resonance; and a persistent sodium current I NaP , which provides amplification of resonance. Responses to injected current revealed that P14 cells were often nonresonant with a relatively high resistance. Densities of I h and I NaP both rose by about 50% from P14 to P18. However, I h levels fell to intermediate values by P28ϩ. Given the nonrobust trend in I h expression and a previously demonstrated potency of even low levels of I h to sustain oscillation, we propose that resonance and MPOs are limited at P14 more by low levels of I NaP than of I h . The relative importance of I NaP for the development of MPOs is supported by simulations of a conductancebased model, which also suggest that general shunt conductance may influence the precise age when MPOs appear. In addition to our physiological study, we analyzed spine densities at P14, P18, and P28ϩ and found a vigorous synaptogenesis across the whole period. Our data predict that functions that rely on theta rhythmicity in the hippocampal network are limited until at least P18.

The Range of Intrinsic Frequencies Represented by Medial Entorhinal Cortex Stellate Cells Extends with Age

“…It is therefore interesting that Burton et al (2008) found a continuous increase in the expression of HCN channels up to the end of their study at P28, although they did not find a clear physiological correlate of this process. This pattern agrees with data by Richter et al (1997) and with our own findings showing age-related acceleration of the sag potential.…”

“…It is usually difficult to dissociate the effects of sensory experience and genetically prescribed patterns of postnatal maturation. Burton et al (2008) found that dendritic spine density of mEC layer II stellate cells increased almost threefold from the second to the fourth postnatal week without changes of stellate cell excitability beyond P18. However, as our data show, the intrinsic excitability continues to change differentially within the population.…”

“…The development of stellate cell excitability in the first postnatal weeks has been recently addressed by Burton et al (2008). Here, we extend their study by investigating the development of the gradient in stellate cell properties from weaning [postnatal days 21-25 (P21-P25) to adulthood when rats most actively explore their environment (Whishaw and Kolb, 2004;McCutcheon and Marinelli, 2009).…”

Activation of Group II Metabotropic Glutamate Receptors Inhibits Glutamatergic Transmission in the Rat Entorhinal Cortex via Reduction of Glutamate Release Probability

“…We have demonstrated that presynaptic stimulation at 5 Hz within the theta frequency (4--12 Hz) induces depression of glutamatergic transmission via activation of mGluR II. Theta oscillations are associated with memory (Buzsaki 2002(Buzsaki , 2005Hasselmo 2006) and are found in the EC (Alonso and Llinas 1989;Burton et al 2008). Whether mGluR II--mediated depression of glutamate release plays a role in mGluR II--mediated modulation of memory still remains to be investigated in the future.…”

Rebound spiking in layer II medial entorhinal cortex stellate cells: Possible mechanism of grid cell function

“…Single neuron models used the framework developed by Izhikevich (2007) with the following equations: $$C\stackrel{.}{v}=k(v-v_r)(v-v_t)-u+(I_b+I)$$$$\stackrel{.}{u}=a\{b(v-v_r)-u\}$$ where v is the membrane potential, u is the current, I b is the baseline holding current, I is the injected current, C is the membrane capacitance (pF), v r is the resting membrane potential (mV), v t is the threshold voltage, k is the fast activation current with a , the fast current and b , the slow current, v peak is the maximum voltage of a spike, c is the reset voltage, and d is the reset current. Parameters were chosen to match previously published values (Izhikevich, 2007) used to replicate properties of stellate cell recordings in mEC (Burton, Economo, Lee, & White, 2008). For all simulations we used the following parameter values: I b = 130, C = 200, v r = −60, v t = −45, k = 0.75, a = 0.007 for low frequency resonance, a = 0.015 for high frequency resonance, b = 14.2, c = −50, d = 100, and v peak = 100.…”