Learning to Learn: Theta Oscillations Predict New Learning, which Enhances Related Learning and Neurogenesis

Animals in the natural world continuously encounter learning experiences of varying degrees of novelty. New neurons in the hippocampus are especially responsive to learning associations between novel events and more cells survive if a novel and challenging task is learned. One might wonder whether new neurons would be rescued from death upon each new learning experience or whether there is an internal control system that limits the number of cells that are retained as a function of learning. In this experiment, it was hypothesized that learning a task that was similar in content to one already learned previously would not increase cell survival. We further hypothesized that in situations in which the cells are rescued hippocampal theta oscillations (3–12 Hz) would be involved and perhaps necessary for increasing cell survival. Both hypotheses were disproved. Adult male Sprague-Dawley rats were trained on two similar hippocampus-dependent tasks, trace and very-long delay eyeblink conditioning, while recording hippocampal local-field potentials. Cells that were generated after training on the first task were labeled with bromodeoxyuridine and quantified after training on both tasks had ceased. Spontaneous theta activity predicted performance on the first task and the conditioned stimulus induced a theta-band response early in learning the first task. As expected, performance on the first task correlated with performance on the second task. However, theta activity did not increase during training on the second task, even though more cells were present in animals that had learned. Therefore, as long as learning occurs, relatively small changes in the environment are sufficient to increase the number of surviving neurons in the adult hippocampus and they can do so in the absence of an increase in theta activity. In conclusion, these data argue against an upper limit on the number of neurons that can be rescued from death by learning

The benefits and challenges of family genetic testing in rare genetic diseases—lessons from Fabry disease

International audienceBackground: Family genetic testing of patients newly diagnosed with a rare genetic disease can improve early diagnosis of family members, allowing patients to receive disease-specific therapies when available. Fabry disease, an X-linked lysosomal storage disorder caused by pathogenic variants in GLA, can lead to end-stage renal disease, cardiac arrhythmias, and stroke. Diagnostic delays are common due to the rarity of the disease and non-specificity of early symptoms. Newborn screening and screening of at-risk populations, (e.g., patients with hypertrophic cardiomyopathy or undiagnosed nephropathies) can identify individuals with Fabry disease. Subsequent cascade genotyping of family members may disclose a greater number of affected individuals, often at younger age than they would have been diagnosed otherwise. Methods: We conducted a literature search to identify all published data on family genetic testing for Fabry disease, and discussed these data, experts’ own experiences with family genetic testing, and the barriers to this type of screening that are present in their respective countries. Results: There are potential barriers that make implementation of family genetic testing challenging in some countries. These include associated costs and low awareness of its importance, and cultural and societal issues. Regionally, there are barriers associated with population educational levels, national geography and infrastructures, and a lack of medical geneticists. Conclusion: In this review, the worldwide experience of an international group of experts of Fabry disease highlights the issues faced in the family genetic testing of patients affected with rare genetic diseases

Behavioral state-dependent episodic representations in rat CA1 neuronal activity during spatial alternation

Hippocampus is considered crucial for episodic memory, as confirmed by recent findings of “episode-dependent place cells” in rodent studies, and is known to show differential activity between active exploration and quiet immobility. Most place-cell studies have focused on active periods, so the hippocampal involvement in episodic representations is less well understood. Here, we draw a typology of episode-dependent hippocampal activity among three behavioral periods, presumably governed by different molecular mechanisms: Active exploration with type 1 theta, quiet alertness with type 2 theta, and consummation with large amplitude irregular activity. Five rats were trained to perform a delayed spatial alternation task with a nose-poke paradigm and 12 tetrodes were implanted for single-unit recordings. We obtained 135 CA1 pyramidal cells and found that 75 of these fired mainly during active exploration, whereas 42 fired mainly during quiet alertness and 18 during consummation. In each type of neuron, we found episode-dependent activity: 51/75, 22/42, and 15/18, respectively. These findings extend our knowledge on the hippocampal involvement in episodic memory: Episode dependency also exists during immobile periods, and functionally dissociated cell assemblies are engaged in the maintenance of episodic information throughout different events in a task sequence

What is different about spinal pain?

<p>Abstract</p> <p>Background</p> <p>The mechanisms subserving deep spinal pain have not been studied as well as those related to the skin and to deep pain in peripheral limb structures. The clinical phenomenology of deep spinal pain presents unique features which call for investigations which can explain these at a mechanistic level.</p> <p>Methods</p> <p>Targeted searches of the literature were conducted and the relevant materials reviewed for applicability to the thesis that deep spinal pain is distinctive from deep pain in the peripheral limb structures. Topics related to the neuroanatomy and neurophysiology of deep spinal pain were organized in a hierarchical format for content review.</p> <p>Results</p> <p>Since the 1980’s the innervation characteristics of the spinal joints and deep muscles have been elucidated. Afferent connections subserving pain have been identified in a distinctive somatotopic organization within the spinal cord whereby afferents from deep spinal tissues terminate primarily in the lateral dorsal horn while those from deep peripheral tissues terminate primarily in the medial dorsal horn. Mechanisms underlying the clinical phenomena of referred pain from the spine, poor localization of spinal pain and chronicity of spine pain have emerged from the literature and are reviewed here, especially emphasizing the somatotopic organization and hyperconvergence of dorsal horn “low back (spinal) neurons”. Taken together, these findings provide preliminary support for the hypothesis that deep spine pain is different from deep pain arising from peripheral limb structures.</p> <p>Conclusions</p> <p>This thesis addressed the question “what is different about spine pain?” Neuroanatomic and neurophysiologic findings from studies in the last twenty years provide preliminary support for the thesis that deep spine pain is different from deep pain arising from peripheral limb structures.</p