-
Annual Review of Cell and Developmental... Oct 2019In spite of the high metabolic cost of cellular production, the brain contains only a fraction of the neurons generated during embryonic development. In the rodent... (Review)
Review
In spite of the high metabolic cost of cellular production, the brain contains only a fraction of the neurons generated during embryonic development. In the rodent cerebral cortex, a first wave of programmed cell death surges at embryonic stages and affects primarily progenitor cells. A second, larger wave unfolds during early postnatal development and ultimately determines the final number of cortical neurons. Programmed cell death in the developing cortex is particularly dependent on neuronal activity and unfolds in a cell-specific manner with precise temporal control. Pyramidal cells and interneurons adjust their numbers in sync, which is likely crucial for the establishment of balanced networks of excitatory and inhibitory neurons. In contrast, several other neuronal populations are almost completely eliminated through apoptosis during the first two weeks of postnatal development, highlighting the importance of programmed cell death in sculpting the mature cerebral cortex.
Topics: Animals; Apoptosis; Cell Differentiation; Cell Proliferation; Humans; Interneurons; Neocortex; Neuroglia; Pyramidal Cells
PubMed: 31283379
DOI: 10.1146/annurev-cellbio-100818-125204 -
PLoS Computational Biology Sep 2022Improving biological plausibility and functional capacity are two important goals for brain models that connect low-level neural details to high-level behavioral...
Improving biological plausibility and functional capacity are two important goals for brain models that connect low-level neural details to high-level behavioral phenomena. We develop a method called "oracle-supervised Neural Engineering Framework" (osNEF) to train biologically-detailed spiking neural networks that realize a variety of cognitively-relevant dynamical systems. Specifically, we train networks to perform computations that are commonly found in cognitive systems (communication, multiplication, harmonic oscillation, and gated working memory) using four distinct neuron models (leaky-integrate-and-fire neurons, Izhikevich neurons, 4-dimensional nonlinear point neurons, and 4-compartment, 6-ion-channel layer-V pyramidal cell reconstructions) connected with various synaptic models (current-based synapses, conductance-based synapses, and voltage-gated synapses). We show that osNEF networks exhibit the target dynamics by accounting for nonlinearities present within the neuron models: performance is comparable across all four systems and all four neuron models, with variance proportional to task and neuron model complexity. We also apply osNEF to build a model of working memory that performs a delayed response task using a combination of pyramidal cells and inhibitory interneurons connected with NMDA and GABA synapses. The baseline performance and forgetting rate of the model are consistent with animal data from delayed match-to-sample tasks (DMTST): we observe a baseline performance of 95% and exponential forgetting with time constant τ = 8.5s, while a recent meta-analysis of DMTST performance across species observed baseline performances of 58 - 99% and exponential forgetting with time constants of τ = 2.4 - 71s. These results demonstrate that osNEF can train functional brain models using biologically-detailed components and open new avenues for investigating the relationship between biophysical mechanisms and functional capabilities.
Topics: Action Potentials; Animals; Models, Neurological; Neurons; Pyramidal Cells; Synapses
PubMed: 36074765
DOI: 10.1371/journal.pcbi.1010461 -
Molecular and Cellular Neurosciences Sep 2020Neurons are highly polarized cells that have specialized regions for synaptic input, the dendrites, and synaptic output, the axons. This polarity is critical for... (Review)
Review
Neurons are highly polarized cells that have specialized regions for synaptic input, the dendrites, and synaptic output, the axons. This polarity is critical for appropriate neural circuit formation and function. One of the central gaps in our knowledge is understanding how developing neurons initiate axon polarity. Given the critical nature of this polarity on neural circuit formation and function, neurons have evolved multiple mechanisms comprised of extracellular and intracellular cues that allow them to initiate and form axons. These mechanisms engage a variety of signaling cascades that provide positive and negative cues to ensure axon polarization. This review highlights our current knowledge of the molecular underpinnings of axon polarization in pyramidal neurons and their relevance to the development of the brain.
Topics: Animals; Axons; Cell Polarity; Dendrites; Humans; Interneurons; Pyramidal Cells; Signal Transduction
PubMed: 32653476
DOI: 10.1016/j.mcn.2020.103522 -
Trends in Cognitive Sciences Jun 2020The first patch-clamp recordings from the dendrites of human neocortical neurons have recently been reported by Beaulieu-Laroche et al. and Gidon et al. These studies...
The first patch-clamp recordings from the dendrites of human neocortical neurons have recently been reported by Beaulieu-Laroche et al. and Gidon et al. These studies have shown that human dendrites are electrically excitable, exhibiting backpropagating action potentials and fast dendritic calcium spikes. This new frontier highlights the potential for interspecies differences in the biophysics of dendritic computation.
Topics: Action Potentials; Dendrites; Humans; Neurons; Patch-Clamp Techniques; Pyramidal Cells
PubMed: 32392467
DOI: 10.1016/j.tics.2020.03.002 -
Nature Neuroscience Aug 2023Genetically defined subgroups of inhibitory interneurons are thought to play distinct roles in learning, but heterogeneity within these subgroups has limited our...
Genetically defined subgroups of inhibitory interneurons are thought to play distinct roles in learning, but heterogeneity within these subgroups has limited our understanding of the scope and nature of their specific contributions. Here we reveal that the chandelier cell (ChC), an interneuron type that specializes in inhibiting the axon-initial segment (AIS) of pyramidal neurons, establishes cortical microcircuits for organizing neural coding through selective axo-axonic synaptic plasticity. We found that organized motor control is mediated by enhanced population coding of direction-tuned premotor neurons, with tuning refined through suppression of irrelevant neuronal activity. ChCs contribute to learning-dependent refinements by providing selective inhibitory control over individual pyramidal neurons rather than global suppression. Quantitative analysis of structural plasticity across axo-axonic synapses revealed that ChCs redistributed inhibitory weights to individual pyramidal neurons during learning. These results demonstrate an adaptive logic of the inhibitory circuit motif responsible for organizing distributed neural representations. Thus, ChCs permit efficient cortical computation in a targeted cell-specific manner.
Topics: Behavior Control; Axons; Neurons; Pyramidal Cells; Synapses; Interneurons
PubMed: 37474640
DOI: 10.1038/s41593-023-01380-x -
Chemical Senses Jan 2021The neocortex and olfactory cortices share many features including their laminar organization, developmental sequences, and cell types. Previous work indicates that...
The neocortex and olfactory cortices share many features including their laminar organization, developmental sequences, and cell types. Previous work indicates that neocortical pyramidal cells exhibit a gradient of dendritic size: cells involved in the initial processing of information are less complex than those in subsequent, higher processing areas. Results presented here confirm that the same is true for the olfactory cortex: pyramidal cells in the region closest to the olfactory bulb, the anterior olfactory nucleus, have smaller total dendritic length and occupy less neural space than those in the posterior piriform cortex. These findings add to the evidence for general rules of development, organization, and function across forebrain cortices.
Topics: Animals; Mice; Olfactory Cortex; Pyramidal Cells
PubMed: 33433589
DOI: 10.1093/chemse/bjab002 -
Nature Neuroscience Apr 2018Hippocampal network operations supporting spatial navigation and declarative memory are traditionally interpreted in a framework where each hippocampal area, such as the... (Review)
Review
Hippocampal network operations supporting spatial navigation and declarative memory are traditionally interpreted in a framework where each hippocampal area, such as the dentate gyrus, CA3, and CA1, consists of homogeneous populations of functionally equivalent principal neurons. However, heterogeneity within hippocampal principal cell populations, in particular within pyramidal cells at the main CA1 output node, is increasingly recognized and includes developmental, molecular, anatomical, and functional differences. Here we review recent progress in the delineation of hippocampal principal cell subpopulations by focusing on radially defined subpopulations of CA1 pyramidal cells, and we consider how functional segregation of information streams, in parallel channels with nonuniform properties, could represent a general organizational principle of the hippocampus supporting diverse behaviors.
Topics: Animals; Electronic Data Processing; Hippocampus; Humans; Neural Pathways; Pyramidal Cells
PubMed: 29593317
DOI: 10.1038/s41593-018-0118-0 -
Reviews in the Neurosciences Dec 2022There is evidence that olfactory cortex responds to its afferent input with the generation of cell assemblies: collections of principal neurons that fire together over a... (Review)
Review
There is evidence that olfactory cortex responds to its afferent input with the generation of cell assemblies: collections of principal neurons that fire together over a time scale of tens of ms. If such assemblies form an odor representation, then a fundamental question is how each assembly then induces neuronal activity in downstream structures. We have addressed this question in a detailed model of superficial layers of lateral entorhinal cortex, a recipient of input from olfactory cortex and olfactory bulb. Our results predict that the response of the fan cell subpopulation can be approximated by a relatively simple Boolean process, somewhat along the lines of the McCulloch/Pitts scheme; this is the case because of the sparsity of recurrent excitation amongst fan cells. However, because of recurrent excitatory connections between layer 2 and layer 3 pyramidal cells, synaptic and probably also gap junctional, the response of pyramidal cell subnetworks cannot be so approximated. Because of the highly structured anatomy of entorhinal output projections, our model suggests that downstream targets of entorhinal cortex (dentate gyrus, hippocampal CA3, CA1, piriform cortex, olfactory bulb) receive differentially processed information.
Topics: Humans; Entorhinal Cortex; Hippocampus; Neurons; Pyramidal Cells
PubMed: 35447022
DOI: 10.1515/revneuro-2022-0011 -
Science Advances Aug 2023The insulin superfamily of peptides is essential for homeostasis as well as neuronal plasticity, learning, and memory. Here, we show that insulin-like growth factors 1...
The insulin superfamily of peptides is essential for homeostasis as well as neuronal plasticity, learning, and memory. Here, we show that insulin-like growth factors 1 and 2 (IGF1 and IGF2) are differentially expressed in hippocampal neurons and released in an activity-dependent manner. Using a new fluorescence resonance energy transfer sensor for IGF1 receptor (IGF1R) with two-photon fluorescence lifetime imaging, we find that the release of IGF1 triggers rapid local autocrine IGF1R activation on the same spine and more than several micrometers along the stimulated dendrite, regulating the plasticity of the activated spine in CA1 pyramidal neurons. In CA3 neurons, IGF2, instead of IGF1, is responsible for IGF1R autocrine activation and synaptic plasticity. Thus, our study demonstrates the cell type-specific roles of IGF1 and IGF2 in hippocampal plasticity and a plasticity mechanism mediated by the synthesis and autocrine signaling of IGF peptides in pyramidal neurons.
Topics: Autocrine Communication; Dendritic Spines; Hippocampus; Neuronal Plasticity; Pyramidal Cells
PubMed: 37531435
DOI: 10.1126/sciadv.adg0666 -
Brain : a Journal of Neurology Jun 2023Memory deficits are a debilitating symptom of epilepsy, but little is known about mechanisms underlying cognitive deficits. Here, we describe a Na+ channel-dependent...
Memory deficits are a debilitating symptom of epilepsy, but little is known about mechanisms underlying cognitive deficits. Here, we describe a Na+ channel-dependent mechanism underlying altered hippocampal dendritic integration, degraded place coding and deficits in spatial memory. Two-photon glutamate uncaging experiments revealed a marked increase in the fraction of hippocampal first-order CA1 pyramidal cell dendrites capable of generating dendritic spikes in the kainate model of chronic epilepsy. Moreover, in epileptic mice dendritic spikes were generated with lower input synchrony, and with a lower threshold. The Nav1.3/1.1 selective Na+ channel blocker ICA-121431 reversed dendritic hyperexcitability in epileptic mice, while the Nav1.2/1.6 preferring anticonvulsant S-Lic did not. We used in vivo two-photon imaging to determine if aberrant dendritic excitability is associated with altered place-related firing of CA1 neurons. We show that ICA-121431 improves degraded hippocampal spatial representations in epileptic mice. Finally, behavioural experiments show that reversing aberrant dendritic excitability with ICA-121431 reverses hippocampal memory deficits. Thus, a dendritic channelopathy may underlie cognitive deficits in epilepsy and targeting it pharmacologically may constitute a new avenue to enhance cognition.
Topics: Mice; Animals; Dendrites; Hippocampus; Acetamides; Pyramidal Cells; Epilepsy; Action Potentials
PubMed: 36448426
DOI: 10.1093/brain/awac455