Neuromodulation of Ih in layer II medial entorhinal cortex stellate cells: a voltage-clamp study

JG Heys, ME Hasselmo - Journal of Neuroscience, 2012 - Soc Neuroscience
Journal of Neuroscience, 2012Soc Neuroscience
Stellate cells in layer II of medial entorhinal cortex (mEC) are endowed with a large
hyperpolarization-activated cation current [h current (I h)]. Recent work using in vivo
recordings from awake behaving rodents demonstrate that I h plays a significant role in
regulating the characteristic spatial periodicity of “grid cells” in mEC. A separate, yet related,
line of research demonstrates that grid field spacing changes as a function of behavioral
context. To understand the neural mechanism or mechanisms that could be underlying …
Stellate cells in layer II of medial entorhinal cortex (mEC) are endowed with a large hyperpolarization-activated cation current [h current (Ih)]. Recent work using in vivo recordings from awake behaving rodents demonstrate that Ih plays a significant role in regulating the characteristic spatial periodicity of “grid cells” in mEC. A separate, yet related, line of research demonstrates that grid field spacing changes as a function of behavioral context. To understand the neural mechanism or mechanisms that could be underlying these changes in grid spacing, we have conducted voltage-clamp recordings of Ih in layer II stellate cells. In particular, we have studied Ih under the influence of several neuromodulators. The results demonstrate that Ih amplitude can be both upregulated and downregulated through activation of distinct neuromodulators in mEC. Activation of muscarinic acetylcholine receptors produces a significant decrease in the Ih tail current and a hyperpolarizing shift in the activation, whereas upregulation of cAMP through application of forskolin produces a significant increase in the Ih amplitude and a depolarizing shift in Ih activation curve. In addition, there was evidence of differential modulation of Ih along the dorsal–ventral axis of mEC. Voltage-clamp protocols were also used to determine whether M current is present in stellate cells. In contrast to CA1 pyramidal neurons, which express M current, the data demonstrate that M current is not present in stellate cells. The results from this study provide key insights into a potential mechanism that could be underlying changes seen in grid field spacing during distinct behavioral contexts.
Soc Neuroscience