Dorsoventral differences in intrinsic properties in developing CA1 pyramidal cells.

The dorsoventral and developmental gradients of entorhinal layer II cell grid properties correlate with their resonance properties and with their hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel current characteristics. We investigated whether such correlation existed in rat hippocampal CA1 pyramidal cells, where place fields also show spatial and temporal gradients. Resonance was absent during the first postnatal week, and emerged during the second week. Resonance was stronger in dorsal than ventral cells, in accord with HCN current properties. Resonance responded to cAMP in ventral but not in dorsal cells. The dorsoventral distribution of HCN1 and HCN2 subunits and of the auxiliary protein tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) could account for these differences between dorsal and ventral cells. The analogous distribution of the intrinsic properties of entorhinal stellate and hippocampal cells suggests the existence of general rules of organization among structures that process complementary features of the environment.

Differential dorso-ventral distributions of Kv4.2 and HCN proteins confer distinct integrative properties to hippocampal CA1 pyramidal cell distal dendrites.

The dorsal and ventral regions of the hippocampus perform different functions. Whether the integrative properties of hippocampal cells reflect this heterogeneity is unknown. We focused on dendrites where most synaptic input integration takes place. We report enhanced backpropagation and theta resonance and decreased summation of synaptic inputs in ventral versus dorsal CA1 pyramidal cell distal dendrites. Transcriptional Kv4.2 down-regulation and post-transcriptional hyperpolarization-activated cyclic AMP-gated channel (HCN1/2) up-regulation may underlie these differences, respectively. Our results reveal differential dendritic integrative properties along the dorso-ventral axis, reflecting diverse computational needs.

Using Monte-Carlo-simulated radiation transport to calculate dose distribution in rats before irradiation with Leksell Gamma Knife 4C: technical note.

BACKGROUND: Gamma knife surgery (GKS) is used at subnecrotic doses for temporal lobe epilepsy (TLE) treatment. Rat models of TLE have been used to probe the mechanisms underlying GKS. Previous GKS studies on rats have used the Leksell GammaPlan (LGP) treatment planning system to determine the irradiation time to achieve the dose to deliver. Since LGP is not designed for such small structures, it is important to calibrate the system for the rat brain. METHODS: We have used a Monte Carlo simulation (MCS) radiation transport scheme, with CT data as anatomical and tissue-specific information, to simulate the dose distribution in a rat brain when using a Leksell Gamma Knife. RESULTS: We show how dose distributions obtained by MCS quantitatively compare to those predicted by LGP, and discuss whether LGP should be used for studies involving rats. The energy deposited when using the 4-mm collimators was calculated for targets on both sides of the rat brain in the dorsal hippocampus, which allowed us to determine the exact time to irradiate rats with a given dose. CONCLUSION: The MCS method used in this study can easily be used for future GKS studies on small animals when accurate dose distributions are required.

h channel-dependent deficit of theta oscillation resonance and phase shift in temporal lobe epilepsy.

I(h) tunes hippocampal CA1 pyramidal cell dendrites to optimally respond to theta inputs (4-12 Hz), and provides a negative time delay to theta inputs. Decreased I(h) activity, as seen in experimental temporal lobe epilepsy (TLE), could significantly alter the response of dendrites to theta inputs. Here we report a progressive erosion of theta resonance and phase lead in pyramidal cell dendrites during epileptogenesis in a rat model of TLE. These alterations were due to decreased I(h) availability, via a decline in HCN1/HCN2 subunit expression resulting in decreased h currents, and altered kinetics of the residual channels. This acquired HCN channelopathy thus compromises temporal coding and tuning to theta inputs in pyramidal cell dendrites. Decreased theta resonance in vitro also correlated with a reduction in theta frequency and power in vivo. We suggest that the neuronal/circuitry changes associated with TLE, including altered I(h)-dependent inductive mechanisms, can disrupt hippocampal theta function.