A gravity-based three-dimensional compass in the mouse brain.

Gravity sensing provides a robust verticality signal for three-dimensional navigation. Head direction cells in the mammalian limbic system implement an allocentric neuronal compass. Here we show that head-direction cells in the rodent thalamus, retrosplenial cortex and cingulum fiber bundle are tuned to conjunctive combinations of azimuth and tilt, i.e. pitch or roll. Pitch and roll orientation tuning is anchored to gravity and independent of visual landmarks. When the head tilts, azimuth tuning is affixed to the head-horizontal plane, but also uses gravity to remain anchored to the allocentric bearings in the earth-horizontal plane. Collectively, these results demonstrate that a three-dimensional, gravity-based, neural compass is likely a ubiquitous property of mammalian species, including ground-dwelling animals.

Memantine prevents acute radiation-induced toxicities at hippocampal excitatory synapses.

Background: Memantine has shown clinical utility in preventing radiation-induced cognitive impairment, but the mechanisms underlying its protective effects remain unknown. We hypothesized that abnormal glutamate signaling causes radiation-induced abnormalities in neuronal structure and that memantine prevents synaptic toxicity. Methods: Hippocampal cultures expressing enhanced green fluorescent protein were irradiated or sham-treated and their dendritic spine morphology assessed at acute (minutes) and later (days) times using high-resolution confocal microscopy. Excitatory synapses, defined by co-localization of the pre- and postsynaptic markers vesicular glutamate transporter 1 and postsynaptic density protein 95, were also analyzed. Neurons were pretreated with vehicle, the N-methyl-d-aspartate-type glutamate receptor antagonist memantine, or the glutamate scavenger glutamate pyruvate transaminase to assess glutamate signaling. For animal studies, Thy-1-YFP mice were treated with whole-brain radiotherapy or sham with or without memantine. Results: Unlike previously reported long-term losses of dendritic spines, we found that the acute response to radiation is an initial increase in spines and excitatory synapses followed by a decrease in spine/synapse density with altered spine dynamics. Memantine pre-administration prevented this radiation-induced synaptic remodeling. Conclusion: These results demonstrate that radiation causes rapid, dynamic changes in synaptic structural plasticity, implicate abnormal glutamate signaling in cognitive dysfunction following brain irradiation, and describe a protective mechanism of memantine.

When does integration of independently acquired temporal relationships take place?

Prior research has found that when subjects independently acquire 2 associations with a common element (e.g., S1-S2 and S2-US), each with its own temporal relationship, they behave as if the 2 unique cues (i.e., S1 and US) have a known temporal relationship despite their never having been paired. This is interpreted as indicative of temporal integration of the memories acquired during Phase 1 and Phase 2 of training based on the element common to both experiences (i.e., S2). There are 2 times at which such integration of independent temporal relationships could plausibly occur: at the time of acquisition of the second relationship or at the time of testing. Three lick-suppression experiments with rats were performed to determine when integration occurs. This question of the moment of temporal integration was assessed by extinguishing the mediating element (S2) between learning of the second temporal relationship and testing of S1. Experiment 1 (using sensory preconditioning) and Experiment 2 (using second-order conditioning) found that this manipulation interfered with behavioral control by S1, suggesting that temporal integration occurred at the time of testing. Experiment 3 used spontaneous recovery, a hallmark phenomenon of extinction, to confirm that the S2-alone presentations in Experiments 1 and 2 attenuated integration as a result of extinction of S2. Implications for the temporal coding hypothesis (e.g., Savastano & Miller, 1998) are discussed.

Spontaneous recovery and ABC renewal from retroactive cue interference.

Two conditioned suppression experiments with rats were conducted to determine whether the spontaneous recovery and renewal that are commonly observed in retroactive outcome interference (e.g., extinction) also occur in retroactive cue interference. Experiment 1 showed that a long delay between Phase 2 (the interfering phase) and testing produces a recovery from the cue interference (i.e., the delay enhanced responding to the target cue trained in Phase 1), which is analogous to the spontaneous recovery effect observed in extinction and other retroactive outcome interference procedures. Experiment 2 showed that, when target and interfering cues are trained in separate contexts and testing occurs in a different but familiar context, a recovery from the cue interference is also observed (i.e., the context shift enhanced responding to the target), which is analogous to ABC renewal from extinction. The results are discussed in terms of the possibility that similar associative mechanisms underlie cue and outcome interference.