Dendrites

Learning and memory require activity-induced changes in dendritic translation, but which mRNAs are involved and how they are regulated are unclear. In this study, to monitor how depolarization impacts local dendritic biology, we employed a dendritically targeted proximity labeling approach followed by crosslinking immunoprecipitation, ribosome profiling and mass spectrometry. Depolarization of primary cortical neurons with KCl or the glutamate agonist DHPG caused rapid reprogramming of dendritic protein expression, where changes in dendritic mRNAs and proteins are weakly correlated. For a subset of pre-localized messages, depolarization increased the translation of upstream open reading frames (uORFs) and their downstream coding sequences, enabling localized production of proteins involved in long-term potentiation, cell signaling and energy metabolism. This activity-dependent translation was accompanied by the phosphorylation and recruitment of the non-canonical translation initiation factor eIF4G2, and the translated uORFs were sufficient to confer depolarization-induced, eIF4G2-dependent translational control. These studies uncovered an unanticipated mechanism by which activity-dependent uORF translational control by eIF4G2 couples activity to local dendritic remodeling.

Since the days of Ramón y Cajal, the vast diversity of neuronal and particularly dendrite morphology has been used to catalog neurons into different classes. Dendrite morphology varies greatly and reflects the different functions performed by different types of neurons. Significant progress has been made in our understanding of how dendrites form and the molecular factors and forces that shape these often elaborately sculpted structures. Here, we review work in the nematode Caenorhabditis elegans that has shed light on the developmental mechanisms that mediate dendrite morphogenesis with a focus on studies investigating ciliated sensory neurons and the highly elaborated dendritic trees of somatosensory neurons. These studies, which combine time-lapse imaging, genetics, and biochemistry, reveal an intricate network of factors that function both intrinsically in dendrites and extrinsically from surrounding tissues. Therefore, dendrite morphogenesis is the result of multiple tissue interactions, which ultimately determine the shape of dendritic arbors.

Learning alters cortical representations and improves perception. Apical tuft dendrites in cortical layer 1, which are unique in their connectivity and biophysical properties, may be a key site of learning-induced plasticity. We used both two-photon and SCAPE microscopy to longitudinally track tuft-wide calcium spikes in apical dendrites of layer 5 pyramidal neurons in barrel cortex as mice learned a tactile behavior. Mice were trained to discriminate two orthogonal directions of whisker stimulation. Reinforcement learning, but not repeated stimulus exposure, enhanced tuft selectivity for both directions equally, even though only one was associated with reward. Selective tufts emerged from initially unresponsive or low-selectivity populations. Animal movement and choice did not account for changes in stimulus selectivity. Enhanced selectivity persisted even after rewards were removed and animals ceased performing the task. We conclude that learning produces long-lasting realignment of apical dendrite tuft responses to behaviorally relevant dimensions of a task.

Hypoglossal motor neurons (MNs) within the medullary hypoglossal nucleus innervate the striated muscles of the intrinsic and extrinsic tongue. Dysfunction of the control of the tongue muscles may lead to problems such as dysphagia, dysphonia and the increased risk of aspiration pneumonia in the elderly. In the human and Fischer 344 (F344) rat motor systems, age-related muscle weakness and behavioural dysfunctions are contemporaneous to MN death. In other neurons, dendritic and mitochondrial degenerations are fundamental pathophysiological components preceding neuronal death. We aimed to determine if dendritic, dendritic spine and dendritic mitochondrial pathology were present in old age. We used golgi-cox and serial block-face scanning electron microscopy (SBFSEM) to evaluate dendritic and mitochondrial morphology, respectively in young (6-month) and old (24-month) female and male F344 rats. Dendritic regression and dendritic spine loss occurs in old age, predominantly in larger hypoglossal MNs. In addition, reduced dendritic mitochondrial volume density and mitochondrial fragmentation are apparent in old age. Our results are consistent with established age-related deficits in F344 rats, including tongue muscle sarcopenia, hypoglossal MN loss and dysphagia. Although more work is needed to determine if synaptic and mitochondrial degenerations are causative for age-related neuromotor dysfunctions, our results suggest that strategies to preserve dendrites and mitochondria may be of therapeutic utility.