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Highlights• A simple equation that predicts voltage in response to distributed synaptic inputs.• Responses to distributed and clustered inputs are largely independent of dendritic length.• Spike rates in various Hodgkin Huxley (HH) like or Leaky Integrate-and-Fire (LIF) models are largely independent of morphology.• Precise spike timing (firing pattern) depends on dendritic morphology.• NeuroMorpho.Org database-wide analysis of the relation between dendritic morphology and electrophysiology.• Our equations set precise input-output relations in realistic dendrite models. 2/57Dendritic constancy Cuntz et al. Abstract 1Reducing neuronal size results in less cell membrane and therefore lower input conductance. 2 Smaller neurons are thus more excitable as seen in their voltage responses to current injections 3 in the soma. However, the impact of a neuron's size and shape on its voltage responses to 4 synaptic activation in dendrites is much less understood. Here we use analytical cable theory 5 to predict voltage responses to distributed synaptic inputs and show that these are entirely 6 independent of dendritic length. For a given synaptic density, a neuron's response depends 7 only on the average dendritic diameter and its intrinsic conductivity. These results remain 8 true for the entire range of possible dendritic morphologies irrespective of any particular 9 arborisation complexity. Also, spiking models result in morphology invariant numbers of 10 action potentials that encode the percentage of active synapses. Interestingly, in contrast to 11 spike rate, spike times do depend on dendrite morphology. In summary, a neuron's excitability 12 in response to synaptic inputs is not affected by total dendrite length. It rather provides a 13 homeostatic input-output relation that specialised synapse distributions, local non-linearities 14 in the dendrites and synaptic plasticity can modulate. Our work reveals a new fundamental 15 principle of dendritic constancy that has consequences for the overall computation in neural 16 circuits. 17

Herein, we report the synthesis and neuroprotective power of some N-substituted C -(dialkoxy)phosphorylated nitrones 4a – g , by studying their ability to increase the cell viability, as well as their capacity to reduce necrosis and apoptosis. We have identified ( Z )- N - tert -butyl-1-(diethoxyphosphoryl)methanimine oxide ( 4e ) as the most potent, nontoxic, and neuroprotective agent, with a high activity against neuronal necrotic cell death, a result that correlates very well with its great capacity for the inhibition of the superoxide production (72%), as well as with the inhibition of lipid peroxidation (62%), and the 5-lipoxygenase activity (45%) at 100 μM concentrations. Thus, nitrone 4e could be a convenient promising compound for further investigation.

Neural stem/progenitor cells (NPCs) generate new neurons in the brain throughout an individual's lifetime in an intricate process called neurogenesis. Neurogenic alterations are a common feature of several adult-onset neurodegenerative diseases. The neuronal ceroid lipofuscinoses (NCLs) are the most common group of inherited neurodegenerative diseases that mainly affect children. Pathological features of the NCLs include accumulation of lysosomal storage material, neuroinflammation and neuronal degeneration, yet the exact cause of this group of diseases remains poorly understood. The function of the CLN5 protein, causative of the CLN5 disease form of NCL, is unknown. In the present study, we sought to examine neurogenesis in the neurodegenerative disorder caused by loss of Cln5. Our findings demonstrate a newly identified crucial role for CLN5 in neurogenesis. We report for the first time that neurogenesis is increased in Cln5-deficient mice, which model the childhood neurodegenerative disorder caused by loss of Cln5. Our results demonstrate that, in Cln5 deficiency, proliferation of NPCs is increased, NPC migration is reduced and NPC differentiation towards the neuronal lineage is increased concomitantly with functional alterations in the NPCs. Moreover, the observed impairment in neurogenesis is correlated with increased expression of the pro-inflammatory cytokine IL-1β. A full understanding of the pathological mechanisms that lead to disease and the function of the NCL proteins are critical for designing effective therapeutic approaches for this devastating neurodegenerative disorder.