Classes Of Pyramidal Cells Research Articles

Landscape of ribosome-engaged transcript isoforms reveals extensive neuronal-cell-class-specific alternative splicing programs

Nervous system function relies on complex assemblies of distinct neuronal cell types with unique anatomical and functional properties instructed by molecular programs. Alternative splicing is a key mechanism for the expansion of molecular repertoires and protein splice isoforms shape neuronal cell surface recognition and function. However, the logic of how alternative splicing programs are arrayed across neuronal cells types is poorly understood. We systematically mapped ribosome-associated transcript isoforms in genetically-defined neuron types of the mouse forebrain. Our dataset provides an extensive resource of transcript diversity across major neuron classes. We find that neuronal transcript isoform profiles reliably distinguish even closely-related classes of pyramidal cells and inhibitory interneurons in the mouse hippocampus and neocortex. These highly specific alternative splicing programs selectively control synaptic proteins and intrinsic neuronal properties. Thus, transcript diversification by alternative splicing is a central mechanism for the functional specification of neuronal cell types and circuits.

Synaptic properties of layer VI inverted pyramidal cells in the rodent somatosensory cortex

The properties of specific cortical cell types enable greater understanding of how cortical microcircuits process and transmit sensory, motor, and cognitive information. Previous reports have characterized the intrinsic properties of the inverted pyramidal cell (IPC) where the most prominent dendrite is orientated towards the cortical white matter. Using whole cell patch clamp recordings from rat and mouse somatosensory cortex in conjunction with electric microstimulation of the white matter we characterized the synaptic inputs onto IPCs and the more common upright pyramidal cell (UPC) in the infragranular layers. Both classes of pyramidal cells received monosynaptic glutamatergic input following white matter stimulation, but varied on a number of parameters. Most prominently, UPCs displayed higher amplitude responses and showed greater rates of depression compared to IPCs. These data reinforce the view that IPCs are a separate functional class of cortical neuron.

Serotonin Differentially Regulates L5 Pyramidal Cell Classes of the Medial Prefrontal Cortex in Rats and Mice.

The prefrontal cortex receives a dense serotonergic innervation that plays an important role in its regulation. However, how serotonin regulates different pyramidal and interneuron cell classes in this area is incompletely understood. Previous work in rats has shown that serotonin differentially regulates two classes of pyramidal cells in layer 5. It excites one class by activating 5-HT2A receptors, whereas it more subtly modulates the integrative properties of the other by co-activating 5-HT1A and 5-HT2A receptors. Here we have used electrophysiological recordings, combined with retrograde labeling and morphological reconstruction, to show that the first cell class corresponds to long range corticofugal neurons and the second corresponds to intratelencephalic neurons. These results suggest that, in rats, serotonin facilitates subcortical output while more subtly modulating cortico-cortical and cortico-striatal output. Interestingly, these results obtained in rats differ from those previously reported for mouse prefrontal cortex. Therefore we reinvestigated the effects of serotonin in mice and confirmed that serotonin predominantly activates inhibitory 5-HT1A receptors on long-range corticofugal cells. Thus serotonin exerts opposite effects on these cells in rats and mice. Finally, we determined whether cortical serotonin responsiveness in mice is regulated during development. Serotonin elicited predominantly depolarizing inward current responses during the early postnatal period, whereas inhibitory 5-HT1A receptor-mediated responses did not become evident until the end of the second postnatal week. These results reveal commonalities as well as unexpected differences in the serotonergic regulation of long-range corticofugal and intratelencephalic neurons of layer 5 in rat and mouse.

Mapping of Functionally Characterized Cell Classes onto Canonical Circuit Operations in Primate Prefrontal Cortex

Microcircuits are composed of multiple cell classes that likely serve unique circuit operations. But how cell classes map onto circuit functions is largely unknown, particularly for primate prefrontal cortex during actual goal-directed behavior. One difficulty in this quest is to reliably distinguish cell classes in extracellular recordings of action potentials. Here we surmount this issue and report that spike shape and neural firing variability provide reliable markers to segregate seven functional classes of prefrontal cells in macaques engaged in an attention task. We delineate an unbiased clustering protocol that identifies four broad spiking (BS) putative pyramidal cell classes and three narrow spiking (NS) putative inhibitory cell classes dissociated by how sparse, bursty, or regular they fire. We speculate that these functional classes map onto canonical circuit functions. First, two BS classes show sparse, bursty firing, and phase synchronize their spiking to 3-7 Hz (theta) and 12-20 Hz (beta) frequency bands of the local field potential (LFP). These properties make cells flexibly responsive to network activation at varying frequencies. Second, one NS and two BS cell classes show regular firing and higher rate with only marginal synchronization preference. These properties are akin to setting tonically the excitation and inhibition balance. Finally, two NS classes fired irregularly and synchronized to either theta or beta LFP fluctuations, tuning them potentially to frequency-specific subnetworks. These results suggest that a limited set of functional cell classes emerges in macaque prefrontal cortex (PFC) during attentional engagement to not only represent information, but to subserve basic circuit operations.

Hippocampal Pyramidal Neurons Comprise Two Distinct Cell Types that Are Countermodulated by Metabotropic Receptors

Relating the function of neuronal cell types to information processing and behavior is a central goal of neuroscience. In the hippocampus, pyramidal cells in CA1 and the subiculum process sensory and motor cues to form a cognitive map encoding spatial, contextual, and emotional information, which they transmit throughout the brain. Do these cells constitute a single class or are there multiple cell types with specialized functions? Using unbiased cluster analysis, we show that there are two morphologically and electrophysiologically distinct principal cell types that carry hippocampal output. We show further that these two cell types are inversely modulated by the synergistic action of glutamate and acetylcholine acting on metabotropic receptors that are central to hippocampal function. Combined with prior connectivity studies, our results support a model of hippocampal processing in which the two pyramidal cell types are predominantly segregated into two parallel pathways that process distinct modalities of information.

Electrophysiological classes of layer 2/3 pyramidal cells in monkey prefrontal cortex

The activity of supragranular pyramidal neurons in the dorsolateral prefrontal cortex (DLPFC) neurons is hypothesized to be a key contributor to the cellular basis of working memory in primates. Therefore, the intrinsic membrane properties, a crucial determinant of a neuron's functional properties, are important for the role of DLPFC pyramidal neurons in working memory. The present study aimed to investigate the biophysical properties of pyramidal cells in layer 2/3 of monkey DLPFC to create an unbiased electrophysiological classification of these cells. Whole cell voltage recordings in the slice preparation were performed in 77 pyramidal cells, and 24 electrophysiological measures of their passive and active intrinsic membrane properties were analyzed. Based on the results of cluster analysis of 16 independent electrophysiological variables, 4 distinct electrophysiological classes of monkey pyramidal cells were determined. Two classes contain regular-spiking neurons with low and high excitability and constitute 52% of the pyramidal cells sampled. These subclasses of regular-spiking neurons mostly differ in their input resistance, minimum current that evoked firing, and current-to-frequency transduction properties. A third class of pyramidal cells includes low-threshold spiking cells (17%), which fire a burst of three-five spikes followed by regular firing at all suprathreshold current intensities. The last class consists of cells with an intermediate firing pattern (31%). These cells have two modes of firing response, regular spiking and bursting discharge, depending on the strength of stimulation and resting membrane potential. Our results show that diversity in the functional properties of DLPFC pyramidal cells may contribute to heterogeneous modes of information processing during working memory and other cognitive operations that engage the activity of cortical circuits in the superficial layers of the DLPFC.

Wireless recording and computational modeling of natural electrosensory input in freely swimming electric fish

Event Abstract Back to Event Wireless recording and computational modeling of natural electrosensory input in freely swimming electric fish Haleh Fotowat1*, Reid R. Harrison2 and Rüdiger Krahe1 1 McGill University, Biology, Canada 2 Intan Technologies, LLC, United States Physiological properties of sensory neurons have evolved to extract features of stimuli that are relevant for guiding animals’ behavior within their natural environment. Therefore, to understand the neural computations that underlie sensory-guided behaviors, it is important to achieve a quantitative understanding of the range of natural stimuli that a given sensory system receives. The South American gymnotiform fish generate an electric field around their body through discharges of an electric organ positioned in their tail. Objects with conductivity different from that of the water, and the electric fields generated by other electric fish create amplitude and phase modulations in the electric field that are sensed by electroreceptors that are distributed all over the skin. The electroreceptor afferents project to the electrosensory lateral line lobe (ELL) in the hindbrain, where they synapse on different classes of pyramidal cells with distinct spatiotemporal tuning properties. Although the anatomy and physiology of the ELL pyramidal neurons is fairly well characterized, the dynamics of the natural inputs they receive, and thus the mechanisms by which they could contribute to behavior remain largely unknown. These dynamics should be measured in freely behaving fish because swimming movements alone cause modulations in the electric field as they result in the movement of the electric organ relative to the electroreceptors. We used a miniature wireless telemetry system, to measure the input to the electroreceptors, the local transdermal potential, at a point on the skin in freely swimming weakly electric fish, Apteronotus leptorhynchus. A pair of video cameras was used to simultaneously monitor the locomotion behavior during these recordings. We developed automatic video tracking software and used a computational model of the electric field to calculate changes in transdermal potential caused by natural swimming movements. Tail bends and body movements relative to boundaries of the tank resulted in low frequency amplitude modulations around the frequency of electric organ discharge (EOD). We found a good agreement between the model and the experimental data. Additionally, using the model, we could estimate amplitude modulations at other points along fish’s body. During social interactions with a second fish, the recorded potential was additionally modulated around the difference between the EOD frequencies of the two fish (beat frequency). The depth of these modulations covered a much larger range than those generated by tail bends and boundaries and was itself modulated over time as a result of relative movement of the two fish. Results from this study shed light on the natural dynamics of electrosensory input and how it varies along fish’s body and can be used to simulate behaviorally relevant sensory stimuli for the further investigation of natural sensory processing. Acknowledgements Thanks to Dr. John Maunsell for his support for this project. Keywords: Natural electrosensory input, weakly electric fish, wireless telemetry Conference: Tenth International Congress of Neuroethology, College Park. Maryland USA, United States, 5 Aug - 10 Aug, 2012. Presentation Type: Poster (but consider for Participant Symposium) Topic: Sensory: Electrosensory Citation: Fotowat H, Harrison RR and Krahe R (2012). Wireless recording and computational modeling of natural electrosensory input in freely swimming electric fish. Conference Abstract: Tenth International Congress of Neuroethology. doi: 10.3389/conf.fnbeh.2012.27.00216 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 29 Apr 2012; Published Online: 07 Jul 2012. * Correspondence: Dr. Haleh Fotowat, McGill University, Biology, Montreal, QC, H3A 1B1, Canada, haleh.fotowat@mcgill.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Haleh Fotowat Reid R Harrison Rüdiger Krahe Google Haleh Fotowat Reid R Harrison Rüdiger Krahe Google Scholar Haleh Fotowat Reid R Harrison Rüdiger Krahe PubMed Haleh Fotowat Reid R Harrison Rüdiger Krahe Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Neocortical layer 6, a review

This review attempts to summarise some of the major areas of neocortical research as it pertains to neocortical layer 6. After a brief summary of the development of this intriguing layer, the major pyramidal cell classes to be found in layer 6 are described and compared. The connections made and received by these different classes of neurones are then discussed and the possible functions of these connections, with particular reference to the shaping of responses in visual cortex and thalamus. Inhibition in layer 6 is discussed where appropriate, but not in great detail. Many types of interneurones are to be found in each cortical layer and layer 6 is no exception, but the functions of each type remain to be elucidated (Gonchar et al., 2007).

Receptive field organization across multiple electrosensory maps. I. Columnar organization and estimation of receptive field size

The electric fish Apteronotus leptorhynchus emits a high-frequency electric organ discharge (EOD) sensed by specialized electroreceptors (P-units). Amplitude modulations (AMs) of the EOD are caused by objects such as prey as well as by social interactions with conspecifics. The firing rate of P-units is modulated by the AMs due to both objects and communication signals. P-units trifurcate as they enter the medulla; they terminate topographically with three maps of the electrosensory lateral line lobe (ELL): the centromedial (CMS), centrolateral (CLS), and lateral (LS) segments. Within each map P-units terminate onto the basal dendrites of pyramidal cells. Anterograde filling of P-units and retrograde filling of the basal bushes of pyramidal cells were used to estimate their respective spreads and spacing in the three maps. These estimates were used to compute the receptive field structure of the pyramidal cells: receptive fields were small in CMS and very large in LS with intermediate values in CLS. There are several classes of pyramidal cells defined by morphological and functional criteria; these cells are organized into columns such that each column contains one member of each class and all cells within a column receive the same P-unit input.

Gamma Oscillatory Firing Reveals Distinct Populations of Pyramidal Cells in the CA1 Region of the Hippocampus

Hippocampal place cells that fire together within the same cycle of theta oscillations represent the sequence of positions (movement trajectory) that a rat traverses on a linear track. Furthermore, it has been suggested that the encoding of these and other types of temporal memory sequences is organized by gamma oscillations nested within theta oscillations. Here, we examined whether gamma-related firing of place cells permits such discrete temporal coding. We found that gamma-modulated CA1 pyramidal cells separated into two classes on the basis of gamma firing phases during waking theta periods. These groups also differed in terms of their spike waveforms, firing rates, and burst firing tendency. During gamma oscillations one group's firing became restricted to theta phases associated with the highest gamma power. Consequently, on the linear track, cells in this group often failed to fire early in theta-phase precession (as the rat entered the place field) if gamma oscillations were present. The second group fired throughout the theta cycle during gamma oscillations, and maintained gamma-modulated firing at different stages of theta-phase precession. Our results suggest that the two different pyramidal cell classes may support different types of population codes within a theta cycle: one in which spike sequences representing movement trajectories occur across subsequent gamma cycles nested within each theta cycle, and another in which firing in synchronized gamma discharges without temporal sequences encode a representation of location. We propose that gamma oscillations during theta-phase precession organize the mnemonic recall of population patterns representing places and movement paths.

Distinct classes of pyramidal cells exhibit mutually exclusive firing patterns in hippocampal area CA3b

It is thought that CA3 pyramidal neurons communicate mainly through bursts of spikes rather than so-called trains of regular firing action potentials. Reports of both burst firing and nonburst firing CA3 cells suggest that they may fire with more than one output pattern. With the use of whole-cell recording methods we studied the firing properties of rat hippocampal pyramidal neurons in vitro within the CA3b subregion and found three distinct types of firing patterns. Approximately 37% of cells were regular firing where spikes generated by minimal current injection (rheobase) were elicited with a short latency and with stronger current intensities trains of spikes exhibited spike frequency adaptation (SFA). Another 46% of neurons exhibited a delayed onset at rheobase with a weakly-adapting firing pattern upon stronger stimulation. The remaining 17% of cells showed a burst-firing pattern, though only elicited in response to strong current injection and spontaneous bursts were never observed. Control experiments indicated that the distinct firing patterns were not due to our particular slicing methods or recording techniques. Finally, computer modeling was used to identify how relative differences in K+ conductances, specifically K(C), K(M), and K(D), between cells contribute to the different characteristics of the three types of firing patterns observed experimentally.

Electrophysiological properties of pyramidal neurons in the rat prefrontal cortex: an in vivo intracellular recording study.

In order to determine the electrophysiological properties of prefrontal cortex pyramidal neurons in vivo, intracellular recordings coupled with neurobiotin injection were performed in anesthetized rats. Three main classes of pyramidal cells were distinguished according to both their firing patterns in response to depolarizing current pulses and the characteristics of their action potentials: regular spiking (RS, n = 71); intrinsic (inactivating) bursting (IB, n = 8); and non-inactivating bursting (NIB, n = 26) cells. RS cells were further subdivided into slow-adapting and fast-adapting types, according to their firing frequency adaptation. IB and fast-adapting RS cells could exhibit different firing patterns depending on the intensity of the depolarizing current. In response to successive depolarizing pulses of a given intensity, NIB and some RS cells showed variations in their firing patterns, probably due to the impact of local synaptic activity. All the labeled neurons were pyramidal cells with an apical dendrite that formed a terminal tuft in layer I. As compared to RS cells, NIB cells had a smaller somatic size and their apical dendritic tuft was less extensive, while IB cells presented a larger somatic size, thicker dendrites and a wider extent of their basal and apical dendritic arborization. In conclusion, we found in the rat prefrontal cortex, in vivo, different electrophysiological classes of pyramidal cells whose output firing patterns depend on interactions between their intrinsic properties and the ongoing synaptic activity.

Identification of principal components in cortical evoked potentials by brief surface cooling

Objectives: The evoked potential recorded by a single electrode in rat's barrel cortex after whisker stimulation was shown to be composed of two main principal components shifted in time by about 3 ms. The purpose of this study was to verify the hypothesis that these components represent activity of supra- and infragranular pyramidal cell classes. Results: Our results show that a brief cooling pulse applied to the cortical surface abolishes the shorter latency component, which may therefore be attributed to the response of supragranular pyramidal cells. Conclusions: The longer latency principal component, which disappears only with strong cooling pulses, is proposed to represent postsynaptic activity of infragranular pyramidal neurons.

Untangling the Web

NEUROSCIENCE Pyramidal cells in layer V of the neocortex form a major excitatory projection system in the brain. Their activity is modulated by a network of excitatory and inhibitory inputs from local intracolumnar neurons and from neurons in other columns. Schubert et al. have analyzed the origin, strength, and spatial distribution of synaptic inputs onto layer V pyramidal cells in the rat somatosensory cortex. Morphologically and functionally, two major classes of pyramidal cells, intrinsically bursting (IB) and regular spiking (RS), were differentiated. Both received excitatory input from all cortical layers. Inputs from layers V and VI were more homogenous, whereas those from layers IV and II/III showed a patchy distribution. Excitatory inputs from layer VI were stronger for IB than for RS cells, and IB cells received only weak inhibitory inputs, mainly of local origin. In contrast, inhibitory inputs onto RS cells were much stronger and originated predominantly from layers II/III and V of the same column and from layer V of the adjacent columns. Thus, the IB cells may be important for integration of excitatory inputs across several cortical columns, and the RS cells may be better suited for information processing within a cortical column. — PRS J. Neurosci. 21 , 3580 (2001).

Spontaneous variability reveals principal components in cortical evoked potentials.

Using principal component analysis, we studied trial to trial, spontaneous variability of evoked potentials (EPs) recorded from rat barrel cortex after whisker stimulation. This method allowed for extraction of two distinct components of EP which overlapped in the time domain. Our results are consonant with the previously described depth distribution of current sources and the extracted components can be therefore attributed to activities of two pyramidal cell classes: supra- and infragranular. Qualitatively similar results were found in both anaesthetized and alert animals.

Repetitive burst-firing neurons in the deep layers of mouse somatosensory cortex

Intracellular recordings were made from neurons of the mouse somatosensory cortex isolated in vitro. Two physiologically distinct classes of pyramidal cells were observed: regular-spiking cells were the majority, and generated accommodating trains of single spikes; bursting cells generated clusters of 2–5 action potentials, and clusters were separated by prolonged afterhyperpolarizations. The bursting cells of the mouse neocortex were unusual in producing repetitive bursting during sustained current pulses, and in being localized to a laminar zone straddling layers V and VI.

Dendritic morphology and axon collaterals of corticotectal, corticopontine, and callosal neurons in layer V of primary visual cortex of the hooded rat.

Recent evidence indicates that corticotectal neurons belong to only one of the three morphological classes of pyramidal cells in layer V. The present study compares the dendritic morphology and axon collaterals of corticotectal, corticopontine, and layer V callosal neurons by using techniques based on the retrograde transport of horseradish peroxidase and fluorescent dyes as well as in vitro intracellular dye injections. Our results indicate that corticotectal and corticopontine neurons are located predominantly in the upper middle part of layer V. These neurons have medium to large somas with 5 or 6 primary basal dendrites and a single apical dendrite ascending to layer I. Approximately 60% of these cells send axon collaterals to both the superior colliculus and the pons. In contrast, callosal neurons form a heterogeneous group. In general, they have small pyramidal or ovoid cell bodies which give rise to 3 or 4 primary basal dendrites. Many cells have an apical dendrite that bifurcates and terminates in layer V or IV. We find that callosal neurons do not send an axon collateral to either the superior colliculus or the pons. We conclude that the corticotectal and corticopontine systems are similar in their intralaminar distribution, dendritic morphology, and pattern of axon collaterals, whereas the callosal system differs in these characteristics.