High synaptic threshold for dendritic NMDA spike generation in human layer 2/3 pyramidal neurons.

Neurons receive synaptic input primarily onto their dendrites. While we know much about the electrical properties of dendrites in rodents, we have only just started to describe their properties in the human brain. Here, we investigate the capacity of human dendrites to generate NMDA-receptor-dependent spikes (NMDA spikes). Using dendritic glutamate iontophoresis, as well as local dendritic synaptic stimulation, we find that human layer 2/3 pyramidal neurons can generate dendritic NMDA spikes. The capacity to evoke NMDA spikes in human neurons, however, was significantly reduced compared with that in rodents. Simulations in morphologically realistic and simplified models indicated that human neurons have a higher synaptic threshold for NMDA spike generation primarily due to the wider diameter of their dendrites. In summary, we find reduced NMDA spike generation in human compared with rodent layer 2/3 pyramidal neurons and provide evidence that this is due to the wider diameter of human dendrites.

The role of higher-order thalamus during learning and correct performance in goal-directed behavior.

The thalamus is a gateway to the cortex. Cortical encoding of complex behavior can therefore only be understood by considering the thalamic processing of sensory and internally generated information. Here, we use two-photon Ca2+ imaging and optogenetics to investigate the role of axonal projections from the posteromedial nucleus of the thalamus (POm) to the forepaw area of the mouse primary somatosensory cortex (forepaw S1). By recording the activity of POm axonal projections within forepaw S1 during expert and chance performance in two tactile goal-directed tasks, we demonstrate that POm axons increase activity in the response and, to a lesser extent, reward epochs specifically during correct HIT performance. When performing at chance level during learning of a new behavior, POm axonal activity was decreased to naive rates and did not correlate with task performance. However, once evoked, the Ca2+ transients were larger than during expert performance, suggesting POm input to S1 differentially encodes chance and expert performance. Furthermore, the POm influences goal-directed behavior, as photoinactivation of archaerhodopsin-expressing neurons in the POm decreased the learning rate and overall success in the behavioral task. Taken together, these findings expand the known roles of the higher-thalamic nuclei, illustrating the POm encodes and influences correct action during learning and performance in a sensory-based goal-directed behavior.

Post-learning paradoxical sleep deprivation impairs reorganization of limbic and cortical networks associated with consolidation of remote contextual fear memory in mice.

Study Objectives: Paradoxical sleep (PS) has been shown to play an important role in memory, in particular in emotional memory processes. However, the involvement of this particular sleep stage in the systemic consolidation of remote (30 days old) memory has never been tested. We examined whether post-learning PS could play a role in the consolidation of remote fearful memory and in the brain network reorganization that depends on it. Methods: Mice were PS-deprived during 6 hours after contextual fear conditioning using an automated method, and their memory was tested either 1 day or 30 days after learning. Brain activity during retrieval was assessed using the immediate early gene Egr1 (Zif 268) as a neuronal marker of activity. Results: We found that PS deprivation impaired the recall of remote (30 days)-but not recent (1 day)-memory. We also showed that the superficial layers of the anterior cingulate cortex were significantly less activated during the retrieval of remote memory after PS deprivation. In contrast, after such deprivation, retrieval of remote memory significantly activated several areas involved in emotional processing such as the CA1 area of the ventral hippocampus, the basolateral amygdala and the superficial layers of the ventral orbitofrontal cortex. By performing graph-theoretical analyses, our result also suggests that post-learning PS deprivation could impact the reorganization of the functional connections between limbic areas in order to reduce the level of global activity in this network. Conclusions: These findings suggest an important role for PS in the systemic consolidation of remote memory.