In both humans and rodents, the external environment is encoded in the form of cognitive maps. Neurons in the medial entorhinal cortex (mEC) represent spatial locations in a sequence of grid-like patterns scaled along the dorsal-ventral axis. The grid spacing correlates with the intrinsic resonance frequencies of stellate cells in layer II of mEC. We investigated the development of frequency preferences in these cells from weaning to adulthood using patch-clamp and sharp microelectrode recordings. We found that the dorsal-ventral gradient of stellate cell properties and frequency preferences exists before animals are able to actively explore their environment. In the transition to adulthood, cells respond faster and become less excitable, and the range of intrinsic resonance frequencies in the population expands in the dorsal direction. This is likely to reflect both the growth of the brain and the expansion of the internal representation caused by new exploratory experience.

Midbrain ventral tegmental neurons project to the prefrontal cortex and modulate cognitive functions. Using viral tracing, optogenetics and electrophysiology, we found that mesocortical neurons in the mouse ventrotegmental area provide fast glutamatergic excitation of GABAergic interneurons in the prefrontal cortex and inhibit prefrontal cortical pyramidal neurons in a robust and reliable manner. These mesocortical neurons were derived from a subset of dopaminergic progenitors, which were dependent on prolonged Sonic Hedgehog signaling for their induction. Loss of these progenitors resulted in the loss of the mesocortical inhibitory circuit and an increase in perseverative behavior, whereas mesolimbic and mesostriatal dopaminergic projections, as well as impulsivity and attentional function, were largely spared. Thus, we identified a previously uncharacterized mesocortical circuit contributing to perseverative behaviors and found that the diversity of dopaminergic neurons begins to be established during their progenitor phase.

The temporal lobe is well known for its oscillatory activity associated with exploration, navigation, and learning. Intrinsic membrane potential oscillations (MPOs) and resonance of stellate cells (SCs) in layer II of the entorhinal cortex are thought to contribute to network oscillations and thereby to the encoding of spatial information. Generation of both MPOs and resonance relies on the expression of specific voltage-dependent ion currents such as the hyperpolarization-activated cation current (I(H)), the persistent sodium current (I(NaP)), and the noninactivating muscarine-modulated potassium current (I(M)). However, the differential contributions of these currents remain a matter of debate. We therefore examined how they modify neuronal excitability near threshold and generation of near-threshold MPOs and resonance in vitro. We found that resonance mainly relied on I(H) and was reduced by I(H) blockers and modulated by cAMP and an I(M) enhancer but that neither of the currents exhibited full control over MPOs in these cells. As previously reported, I(H) controlled a theta-frequency component of MPOs such that blockade of I(H) resulted in fewer regular oscillations that retained low-frequency components and high peak amplitude. However, pharmacological inhibition and augmentation of I(M) also affected MPO frequencies and amplitudes. In contrast to other cell types, inhibition of I(NaP) did not result in suppression of MPOs but only in a moderation of their properties. We reproduced the experimentally observed effects in a single-compartment stochastic model of SCs, providing further insight into the interactions between different ionic conductances.

Astrocytes form large networks, in which individual cells are connected via gap junctions. It is thought that this astroglial gap junction coupling contributes to the buffering of extracellular K+ increases. However, it is largely unknown how the control of extracellular K+ by astroglial gap junction coupling depends on the underlying activity patterns and on the magnitude of extracellular K+ increases. We explored this dependency in acute hippocampal slices (CA1, stratum radiatum) by direct K+‐sensitive microelectrode recordings and acute pharmacological inhibition of gap junctions. K+ transients evoked by synaptic and axonal activity were largely unaffected by acute astroglial uncoupling in slices obtained from young and adult rats. Iontophoretic K+‐application enabled us to generate K+ gradients with defined spatial properties and magnitude. By varying the K+‐iontophoresis position and protocol, we found that acute pharmacological uncoupling increases the amplitude of K+ transients once their initial amplitude exceeded ~10 mM. Our experiments demonstrate that the contribution of gap junction coupling to buffering of extracellular K+ gradients is limited to large and localized K+ increases.