Rapid Arrival and Integration of Ascending Sensory Information in Layer 1 Nonpyramidal Neurons and Tuft Dendrites of Layer 5 Pyramidal Neurons of the Neocortex

AbstractThe rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. Layer 5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of layer 5a in the development of the barrel cortex remains unclear. Previously, we found that calretinin is dynamically expressed in layer 5a. In this study, we analyzed calretinin KO mice and found that the dendritic complexity and length of layer 5a pyramidal neurons were significantly decreased after calretinin ablation. The membrane excitability and excitatory synaptic transmission of layer 5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, layer 4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Calretinin KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of layer 5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.

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FosGFP expression does not capture a sensory learning-related engram in superficial layers of mouse barrel cortex

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2112212118 ◽

2021 ◽

Vol 118 (52) ◽

pp. e2112212118

Author(s):

Jiseok Lee ◽

Joanna Urban-Ciecko ◽

Eunsol Park ◽

Mo Zhu ◽

Stephanie E. Myal ◽

...

Keyword(s):

Pyramidal Neurons ◽

Barrel Cortex ◽

Sensory Information ◽

Learning Task ◽

Early Gene ◽

Sensory Stimuli ◽

Association Learning ◽

Neural Ensembles ◽

Dependent Learning

Immediate-early gene (IEG) expression has been used to identify small neural ensembles linked to a particular experience, based on the principle that a selective subset of activated neurons will encode specific memories or behavioral responses. The majority of these studies have focused on “engrams” in higher-order brain areas where more abstract or convergent sensory information is represented, such as the hippocampus, prefrontal cortex, or amygdala. In primary sensory cortex, IEG expression can label neurons that are responsive to specific sensory stimuli, but experience-dependent shaping of neural ensembles marked by IEG expression has not been demonstrated. Here, we use a fosGFP transgenic mouse to longitudinally monitor in vivo expression of the activity-dependent gene c-fos in superficial layers (L2/3) of primary somatosensory cortex (S1) during a whisker-dependent learning task. We find that sensory association training does not detectably alter fosGFP expression in L2/3 neurons. Although training broadly enhances thalamocortical synaptic strength in pyramidal neurons, we find that synapses onto fosGFP+ neurons are not selectively increased by training; rather, synaptic strengthening is concentrated in fosGFP− neurons. Taken together, these data indicate that expression of the IEG reporter fosGFP does not facilitate identification of a learning-specific engram in L2/3 in barrel cortex during whisker-dependent sensory association learning.

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Heterogeneity of Phasic Cholinergic Signaling in Neocortical Neurons

Journal of Neurophysiology ◽

10.1152/jn.00493.2006 ◽

2007 ◽

Vol 97 (3) ◽

pp. 2215-2229 ◽

Cited By ~ 118

Author(s):

Allan T. Gulledge ◽

Susanna B. Park ◽

Yasuo Kawaguchi ◽

Greg J. Stuart

Keyword(s):

Visual Cortex ◽

Calcium Release ◽

Pyramidal Neurons ◽

Potassium Conductance ◽

Projection Neurons ◽

Sk Channels ◽

Cortical Areas ◽

Neocortical Neurons ◽

Cholinergic Signaling ◽

Nonpyramidal Neurons

Acetylcholine (ACh) is a neurotransmitter critical for normal cognition. Here we demonstrate heterogeneity of cholinergic signaling in neocortical neurons in the rat prefrontal, somatosensory, and visual cortex. Focal ACh application (100 μM) inhibited layer 5 pyramidal neurons in all cortical areas via activation of an apamin-sensitive SK-type calcium-activated potassium conductance. Cholinergic inhibition was most robust in prefrontal layer 5 neurons, where it relies on the same signal transduction mechanism (M1-like receptors, IP3-dependent calcium release, and SK-channels) as exists in somatosensory pyramidal neurons. Pyramidal neurons in layer 2/3 were less responsive to ACh, but substantial apamin-sensitive inhibitory responses occurred in deep layer 3 neurons of the visual cortex. ACh was only inhibitory when presented near the somata of layer 5 pyramidal neurons, where repetitive ACh applications generated discrete inhibitory events at frequencies of up to ∼0.5 Hz. Fast-spiking (FS) nonpyramidal neurons in all cortical areas were unresponsive to ACh. When applied to non-FS interneurons in layers 2/3 and 5, ACh generated mecamylamine-sensitive nicotinic responses (38% of cells), apamin-insensitive hyperpolarizing responses, with or without initial nicotinic depolarization (7% of neurons), or no response at all (55% of cells). Responses in interneurons were similar across cortical layers and regions but were correlated with cellular physiology and the expression of biochemical markers associated with different classes of nonpyramidal neurons. Finally, ACh generated nicotinic responses in all layer 1 neurons tested. These data demonstrate that phasic cholinergic input can directly inhibit projection neurons throughout the cortex while sculpting intracortical processing, especially in superficial layers.

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Altered White Matter and Layer VIb Neurons in Heterozygous Disc1 Mutant, a Mouse Model of Schizophrenia

Frontiers in Neuroanatomy ◽

10.3389/fnana.2020.605029 ◽

2020 ◽

Vol 14 ◽

Author(s):

Shin-Hwa Tsai ◽

Chih-Yu Tsao ◽

Li-Jen Lee

Keyword(s):

White Matter ◽

Mouse Model ◽

Pyramidal Neurons ◽

Sensory Information ◽

Morphological Characters ◽

Cortical Layer ◽

Type I ◽

Brain Functions ◽

Neuron Density ◽

Subplate Neurons

Increased white matter neuron density has been associated with neuropsychiatric disorders including schizophrenia. However, the pathogenic features of these neurons are still largely unknown. Subplate neurons, the earliest generated neurons in the developing cortex have also been associated with schizophrenia and autism. The link between these neurons and mental disorders is also not well established. Since cortical layer VIb neurons are believed to be the remnant of subplate neurons in the adult rodent brain, in this study, we aimed to examine the cytoarchitecture of neurons in cortical layer VIb and the underlying white matter in heterozygous Disc1 mutant (Het) mice, a mouse model of schizophrenia. In the white matter, the number of NeuN-positive neurons was quite low in the external capsule; however, the density of these cells was found increased (54%) in Het mice compared with wildtype (WT) littermates. The density of PV-positive neurons was unchanged in the mutants. In the cortical layer VIb, the density of CTGF-positive neurons increased (21.5%) in Het mice, whereas the number of Cplx3-positive cells reduced (16.1%) in these mutants, compared with WT mice. Layer VIb neurons can be classified by their morphological characters. The morphology of Type I pyramidal neurons was comparable between genotypes while the dendritic length and complexity of Type II multipolar neurons were significantly reduced in Het mice. White matter neurons and layer VIb neurons receive synaptic inputs and modulate the process of sensory information and sleep/arousal pattern. Aberrances of these neurons in Disc1 mutants implies altered brain functions in these mice.

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Loss of Calretinin in L5a Impairs the Formation of the Barrel Cortex Leading to Abnormal Behaviors

10.21203/rs.3.rs-233483/v1 ◽

2021 ◽

Author(s):

Mingzhao Su ◽

Junhua Liu ◽

Baocong Yu ◽

Kaixing Zhou ◽

Congli Sun ◽

...

Keyword(s):

Information Integration ◽

Pyramidal Neurons ◽

Barrel Cortex ◽

Sensory Information ◽

Membrane Excitability ◽

Novelty Preference ◽

Abnormal Behaviors ◽

Dendritic Complexity ◽

Cortex System

Abstract The rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. L5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of L5a in the development of the barrel cortex remains unclear. Previously, we found that Calretinin is dynamically expressed in L5a. In this study, we analyzed Cr KO mice and found that the dendritic complexity and length of L5a pyramidal neurons were significantly decreased after Cr ablation. The membrane excitability and excitatory synaptic transmission of L5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, L4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Cr KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of L5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.

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Morphometric characteristics of Neuropeptide Y immunoreactive neurons of human cortical amygdaloid nucleus

Medicinski pregled ◽

10.2298/mpns0806235m ◽

2008 ◽

Vol 61 (5-6) ◽

pp. 235-241

Author(s):

Milos Malis ◽

Valentina Nikolic ◽

Vuk Djulejic ◽

Dejan Opric ◽

Lukas Rasulic ◽

...

Keyword(s):

Pyramidal Neurons ◽

Dendritic Arborization ◽

Amygdaloid Complex ◽

Amygdaloid Nucleus ◽

Morphometric Characteristics ◽

Male Adult ◽

Moderate Number ◽

Triangular Shape ◽

Nonpyramidal Neurons ◽

Human Brains

Introduction Cortical amygdaloid nucleus belongs to the corticomedial part of the amygdaloid complex. In this nucleus there are neurons that produce neuropetide Y. This peptide has important roles in sleeping, learning, memory, gastrointestinal regulation, anxiety, epilepsy, alcoholism and depression. Material and methods We investigated morphometric characteristics (numbers of primary dendrites, longer and shorter diameters of cell bodies and maximal radius of dendritic arborization) of NPY immunoreactive neurons of human cortical amygdaloid nucleus on 6 male adult human brains, aged 46 to 77 years, by immunohistochemical avidin-biotin technique. Results Our investigation has shown that in this nucleus there is a moderate number of NPY immunoreactive neurons. 67% of found neurons were nonpyramidal, while 33% were pyramidal. Among the nonpyramidal neurons the dominant groups were multipolar neurons (41% - of which 25% were multipolar irregular, and 16% multipolar oval). Among the pyramidal neurons the dominant groups were the neurons with triangular shape of cell body (21%). All found NPY immunoreactive neurons (pyramidal and nonpyramidal altogether) had intervals of values of numbers of primary dendrites 2 to 6, longer diameters of cell bodies 13 to 38 ?m, shorter diameters of cell bodies 9 to 20 ?m and maximal radius of dendritic arborization 50 to 340 ?m. More than a half of investigated neurons (57%) had 3 primary dendrites. Discussion and conclusion The other researchers did not find such percentage of pyramidal immunoreactive neurons in this amygdaloid nucleus. If we compare our results with the results of the ather researchers we can conclude that all pyramidal NPY immunoreactive neurons found in this human amygdaloid nucleus belong to the class I of neurons, and that all nonpyramidal NPY immunoreactive neurons belong to the class II of neurons described by other researchers. We suppose that all found pyramidal neurons were projectional.

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Cholinergic modulation of sensory processing in awake mouse cortex

Scientific Reports ◽

10.1038/s41598-021-96696-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Javier Jimenez-Martin ◽

Daniil Potapov ◽

Kay Potapov ◽

Thomas Knöpfel ◽

Ruth M. Empson

Keyword(s):

Pyramidal Neurons ◽

Brain Activity ◽

Critical Role ◽

Sensory Information ◽

Sensory Stimulation ◽

Cholinergic Modulation ◽

Neuronal Populations ◽

Mouse Cortex ◽

Cortical Pyramidal Neurons ◽

Sensory Evoked

AbstractCholinergic modulation of brain activity is fundamental for awareness and conscious sensorimotor behaviours, but deciphering the timing and significance of acetylcholine actions for these behaviours is challenging. The widespread nature of cholinergic projections to the cortex means that new insights require access to specific neuronal populations, and on a time-scale that matches behaviourally relevant cholinergic actions. Here, we use fast, voltage imaging of L2/3 cortical pyramidal neurons exclusively expressing the genetically-encoded voltage indicator Butterfly 1.2, in awake, head-fixed mice, receiving sensory stimulation, whilst manipulating the cholinergic system. Altering muscarinic acetylcholine function re-shaped sensory-evoked fast depolarisation and subsequent slow hyperpolarisation of L2/3 pyramidal neurons. A consequence of this re-shaping was disrupted adaptation of the sensory-evoked responses, suggesting a critical role for acetylcholine during sensory discrimination behaviour. Our findings provide new insights into how the cortex processes sensory information and how loss of acetylcholine, for example in Alzheimer’s Disease, disrupts sensory behaviours.

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Glutamatergic Nonpyramidal Neurons From Neocortical Layer VI and Their Comparison With Pyramidal and Spiny Stellate Neurons

Journal of Neurophysiology ◽

10.1152/jn.91094.2008 ◽

2009 ◽

Vol 101 (2) ◽

pp. 641-654 ◽

Cited By ~ 38

Author(s):

Sofija Andjelic ◽

Thierry Gallopin ◽

Bruno Cauli ◽

Elisa L. Hill ◽

Lisa Roux ◽

...

Keyword(s):

Pyramidal Neurons ◽

Glutamate Transporter ◽

Gabaergic Interneuron ◽

Acid Decarboxylase ◽

Projection Neurons ◽

Heterogeneous Cluster ◽

Glutamatergic Neurons ◽

Layer V ◽

Nonpyramidal Neurons ◽

Layer Vi

The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription–polymerase chain reaction, and biocytin labeling. The majority of these neurons expressed the vesicular glutamate transporter but not glutamic acid decarboxylase, suggesting that a high proportion of layer VI nonpyramidal neurons are glutamatergic. Indeed, they exhibited numerous dendritic spines and established asymmetrical synapses. Our sample of glutamatergic nonpyramidal neurons displayed a wide variety of somatodendritic morphologies and a subset of these cells expressed the Nurr1 mRNA, a marker for ipsilateral, but not commissural corticocortical projection neurons in layer VI. Comparison with spiny stellate and pyramidal neurons from other layers showed that glutamatergic neurons consistently exhibited a low occurrence of GABAergic interneuron markers and regular spiking firing patterns. Analysis of electrophysiological diversity using unsupervised clustering disclosed three groups of cells. Layer V pyramidal neurons were segregated into a first group, whereas a second group consisted of a subpopulation of layer VI neurons exhibiting tonic firing. A third heterogeneous cluster comprised spiny stellate, layer II/III pyramidal, and layer VI neurons exhibiting adaptive firing. The segregation of layer VI neurons in two different clusters did not correlate either with their somatodendritic morphologies or with Nurr1 expression. Our results suggest that electrophysiological similarities between neocortical glutamatergic neurons extend beyond layer positioning, somatodendritic morphology, and projection specificity.

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Context-dependent decision making in a premotor circuit

10.1101/757104 ◽

2019 ◽

Cited By ~ 2

Author(s):

Zheng Wu ◽

Ashok Litwin-Kumar ◽

Philip Shamash ◽

Alexei Taylor ◽

Richard Axel ◽

...

Keyword(s):

Pyramidal Neurons ◽

Contextual Information ◽

Sensory Information ◽

Behavioral Responses ◽

Association Cortex ◽

Match To Sample ◽

Subsequent Test ◽

Layer 2 ◽

Test Odor ◽

Context Dependent

SummaryCognitive capacities afford contingent associations between sensory information and behavioral responses. We studied this problem using an olfactory delayed match to sample task whereby a sample odor specifies the association between a subsequent test odor and rewarding action. Multi-neuron recordings revealed representations of the sample and test odors in olfactory sensory and association cortex, which were sufficient to identify the test odor as match/non-match. Yet, inactivation of a downstream premotor area (ALM), but not orbitofrontal cortex, confined to the epoch preceding the test odor, led to gross impairment. Olfactory decisions that were not context dependent were unimpaired. Therefore, ALM may not receive the outcome of a match/non-match decision from upstream areas but contextual information—the identity of the sample—to establish the mapping between test odor and action. A novel population of pyramidal neurons in ALM layer 2 may mediate this process.

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