Ion Channel Density Regulates Switches between Regular and Fast Spiking in Soma but Not in Axons

The threshold firing frequency of a neuron is a characterizing feature of its dynamical behaviour, in turn determining its role in the oscillatory activity of the brain. Two main types of dynamics have been identified in brain neurons. Type 1 dynamics (regular spiking) shows a continuous relationship between frequency and stimulation current (f-Istim) and, thus, an arbitrarily low frequency at threshold current; Type 2 (fast spiking) shows a discontinuous f-Istim relationship and a minimum threshold frequency. In a previous study of a hippocampal neuron model, we demonstrated that its dynamics could be of both Type 1 and Type 2, depending on ion channel density. In the present study we analyse the effect of varying channel density on threshold firing frequency on two well-studied axon membranes, namely the frog myelinated axon and the squid giant axon. Moreover, we analyse the hippocampal neuron model in more detail. The models are all based on voltage-clamp studies, thus comprising experimentally measurable parameters. The choice of analysing effects of channel density modifications is due to their physiological and pharmacological relevance. We show, using bifurcation analysis, that both axon models display exclusively Type 2 dynamics, independently of ion channel density. Nevertheless, both models have a region in the channel-density plane characterized by an N-shaped steady-state current-voltage relationship (a prerequisite for Type 1 dynamics and associated with this type of dynamics in the hippocampal model). In summary, our results suggest that the hippocampal soma and the two axon membranes represent two distinct kinds of membranes; membranes with a channel-density dependent switching between Type 1 and 2 dynamics, and membranes with a channel-density independent dynamics. The difference between the two membrane types suggests functional differences, compatible with a more flexible role of the soma membrane than that of the axon membrane

Relationships between structure, in vivo function and long-range axonal target of cortical pyramidal tract neurons

Pyramidal tract neurons (PTs) represent the major output cell type of the neocortex. To investigate principles of how the results of cortical processing are broadcasted to different downstream targets thus requires experimental approaches, which provide access to the in vivo electrophysiology of PTs, whose subcortical target regions are identified. On the example of rat barrel cortex (vS1), we illustrate that retrograde tracer injections into multiple subcortical structures allow identifying the long-range axonal targets of individual in vivo recorded PTs. Here we report that soma depth and dendritic path lengths within each cortical layer of vS1, as well as spiking patterns during both periods of ongoing activity and during sensory stimulation, reflect the respective subcortical target regions of PTs. We show that these cellular properties result in a structure–function parameter space that allows predicting a PT’s subcortical target region, without the need to inject multiple retrograde tracers

Nature Communications

Pyramidal tract neurons (PTs) represent the major output cell type of the neocortex. To investigate principles of how the results of cortical processing are broadcasted to different downstream targets thus requires experimental approaches, which provide access to the in vivo electrophysiology of PTs, whose subcortical target regions are identified. On the example of rat barrel cortex (vS1), we illustrate that retrograde tracer injections into multiple subcortical structures allow identifying the long-range axonal targets of individual in vivo recorded PTs. Here we report that soma depth and dendritic path lengths within each cortical layer of vS1, as well as spiking patterns during both periods of ongoing activity and during sensory stimulation, reflect the respective subcortical target regions of PTs. We show that these cellular properties result in a structure-function parameter space that allows predicting a PT's subcortical target region, without the need to inject multiple retrograde tracers.The major output cell type of the neocorte

Structural basis of sensory-motor control

The rodent vibrissal system offers an ideal model for studying sensory-motor pathways of the central nervous system. There has been much consideration given to bring insight to the organization of the whisker sensory pathways in the rodent brain. However, the organization of the vibrissa motor output pathway and the integration of sensory inputs involved in whisker movement are not completely understood. The goal of our research is to use the rodent whisker system to understand the functional architecture of the cortical and sub-cortical areas involved with whisker motor output generation. Combining trans-synaptic virus injections with custom-designed brain-wide imaging and analysis we generate an unbiased map of all vibrissal motor pathways. Wild-type rabies virus is deposited into the intrinsic and extrinsic musculature of the mystacial pad, targeting a single whisker. The virus is then transported in a time dependent manner throughout the central nervous system via vibrissa motor neurons, located in the lateral area of the facial nucleus that directly innervate the whisker muscles. This technique and the unique features of the virus allow us to provide first-time understanding of the structural basis for sensory-motor whisker control

Reverse engineering sensory perception and decision making: Bridging physiology, anatomy and behavior

Understanding how the brain is able to transform sensory input into decisions is one of the major challenges of systems neuroscience. While recording/imaging during sensory-motor tasks identified neural substrates of sensation and action in various cortical areas, the crucial questions of 1) how these correlates are implemented within the underlying neural networks and 2) how their output triggers decisions, will only be answered when the individual functional measurements are integrated into a coherent model of all task-related circuits. The goal of our research is to use the rodent vibrissal system for building such a model in the context of how a tactile-mediated percept is encoded by the interplay between biophysical, cellular and network mechanisms. Specifically, rodents decide to cross a gap when detecting its far side with a single facial whisker. This suggests that whisker contact with the platform, if synchronized with an internal motor signal, triggers the decision. To test this hypothesis, we will determine all sensory/motor-related local and long-range whisker pathways, measure whisker-evoked responses of these populations and use the data to constrain network simulations of active whisker touch. Using a multidisciplinary approach, combining in vivo electrophysiology, virus injections, custom imaging/reconstruction tools and Monte Carlo simulations, our reverse engineering strategy will provide unmatched mechanistic insight to perceptual decision making and will function as a show case - generalizable across sensory modalities and species - of how to derive computations that underlie behavior

Relationships between sensory-evoked synaptic input and long-range target-related spiking output of cortical layer 5

Even the simplest stimuli evoke highly heterogeneous responses in thousands of neurons in the related primary sensory areas of the mammalian neocortex. This intracortical (IC) representation of the stimulus is integrated by specific output populations in cortical layer 5 (L5), which transmit the results of cortical sensory information processing to several distant brain areas. How local IC activity is transformed into cortical output, and whether the transformations are related to the specific long-range targets is unknown. Here we combined injections of retrograde tracer agents with in vivo recordings and computational modeling to determine relationships between local synaptic input and sensory-evoked responses of individual L5 neurons with identified subcortical targets. We found that cortico-subcortical (CS) neurons in L5 of rat primary somatosensory cortex (S1) are subdivided into four disjoint projection types, which are embedded into the cortical circuitry in a target-related manner. Our results demonstrate that several CS output channels, in parallel, transform IC activity into target-related spiking patterns, potentially to extract disjoint features from the same stimulus

Stochastic

resonance in the spinal cord and somatosensory cortex of the ca

Cell type-specific subcortical targets of layer 5 projecting neurons in the rat vibrissal cortex

Layer 5 pyramidal neurons provide the mayor output of the cortex and consequently likely to be important modulators of sensory and motor processes. This subcortical layer 5 projecting neurons are morphologically and physiologically heterogeneous and project to distinct intracortical and subcortical targets. However, since most of physiological and morphological studies of layer 5 pyramidal neurons have been carried out in unidentified cells, little is known about morphological characteristics related to subcortical projection site. This is important to understand the specificity at single cell level between structural and functional properties in vivo in the mammalian brain. Here, we use retrograde neuronal tracing to analyze the distribution of different populations of subcortical projecting neurons in the rat barrel field somatosensory cortex (BFSI). Additionally, we combine retrograde neuronal tracing with whole cell and juxtacellular recordings in order to fill and reconstruct 3D patterns of functional identified neurons and distinguish special morphological characteristics of each cell type. In this way, we provide unprecedented insight into cell type-specific structural and sensory-evoked functional properties of long-range projection neurons in layer 5 of rat vibrissal cortex

Modulation of synaptic transmission from segmental afferents by spontaneous activity of dorsal horn spinal neurones in the cat

We examined, in the anaesthetised cat, the influence of the neuronal ensembles producing spontaneous negative cord dorsum potentials (nCDPs) on segmental pathways mediating primary afferent depolarisation (PAD) of cutaneous and group I muscle afferents and on Ia monosynaptic activation of spinal motoneurones.The intraspinal distribution of the field potentials associated with the spontaneous nCDPs indicated that the neuronal ensembles involved in the generation of these potentials were located in the dorsal horn of lumbar segments, in the same region of termination of low-threshold cutaneous afferents.During the occurrence of spontaneous nCDPs, transmission from low-threshold cutaneous afferents to second order neurones in laminae III-VI, as well as transmission along pathways mediating PAD of cutaneous and Ib afferents, was facilitated. PAD of Ia afferents was instead inhibited.Monosynaptic reflexes of flexors and extensors were facilitated during the spontaneous nCDPs. The magnitude of the facilitation was proportional to the amplitude of the ‘conditioning’ spontaneous nCDPs. This led to a high positive correlation between amplitude fluctuations of spontaneous nCDPs and fluctuations of monosynaptic reflexes.Stimulation of low-threshold cutaneous afferents transiently reduced the probability of occurrence of spontaneous nCDPs as well as the fluctuations of monosynaptic reflexes.It is concluded that the spontaneous nCDPs were produced by the activation of a population of dorsal horn neurones that shared the same functional pathways and involved the same set of neurones as those responding monosynaptically to stimulation of large cutaneous afferents. The spontaneous activity of these neurones was probably the main cause of the fluctuations of the monosynaptic reflexes observed under anaesthesia and could provide a dynamic linkage between segmental sensory and motor pathways