Tatiana Bezdudnaya

Encoding of Stimulus Frequency and Sensor Motion in the Posterior Medial Thalamic Nucleus

In all sensory systems, information is processed along several parallel streams. In the vibrissa-to-barrel cortex system, these include the lemniscal system and the lesser-known paralemniscal system. The posterior medial nucleus (POm) is the thalamic structure associated with the latter pathway. Previous studies suggested that POm response latencies are positively correlated with stimulation frequency and negatively correlated with response duration, providing a basis for a phase locked loop-temporal decoding of stimulus frequency. We tested this hypothesis by analyzing response latencies of POm neurons, in both awake and anesthetized rats, to vibrissae deflections at frequencies between 0.3 and 11 Hz. We found no significant, systematic correlation between stimulation frequency and the latency or duration of POm responses. We obtained similar findings from recording in awake rats, in rats under different anesthetics, and in anesthetized rats in which the reticular activating system was stimulated. These findings suggest that stimulus frequency is not reliably reflected in response latency of POm neurons. We also tested the hypothesis that POm neurons respond preferentially to sensor motion, that is, they respond to whisking in air, without contacts. We recorded from awake, head-restrained rats while monitoring vibrissae movements. All POm neurons responded to passive whisker deflections, but none responded to noncontact whisking. Thus like their counterparts in the trigeminal ganglion, POm neurons may not reliably encode whisking kinematics. These observations suggest that POm neurons might not faithfully encode vibrissae inputs to provide reliable information on vibrissae movements or contacts.

Brain state and contrast sensitivity in the awake visual thalamus

Neuronal responses to visual stimuli depend on both the nature of the stimulus and brain state. Here we examined the contrast sensitivity of visual thalamic neurons as awake rabbits shifted between alert and nonalert states. We found that despite a large increase in response gain with alertness, contrast sensitivity remained nearly constant. This accurate scaling might be achieved through a balanced increase in excitation and inhibition with alertness.

Laterodorsal nucleus of the thalamus: A processor of somatosensory inputs.

The laterodorsal (LD) nucleus of the thalamus has been considered a “higher order” nucleus that provides inputs to limbic cortical areas. Although its functions are largely unknown, it is often considered to be involved in spatial learning and memory. Here we provide evidence that LD is part of a hitherto unknown pathway for processing somatosensory information. Juxtacellular and extracellular recordings from LD neurons reveal that they respond to vibrissa stimulation with short latency (median = 7 ms) and large magnitude responses (median = 1.2 spikes/stimulus). Most neurons (62%) had large receptive fields, responding to six and more individual vibrissae. Electrical stimulation of the trigeminal nucleus interpolaris (SpVi) evoked short latency responses (median = 3.8 ms) in vibrissa‐responsive LD neurons. Labeling produced by anterograde and retrograde neuroanatomical tracers confirmed that LD neurons receive direct inputs from SpVi. Electrophysiological and neuroanatomical analyses revealed also that LD projects upon the cingulate and retrosplenial cortex, but has only sparse projections to the barrel cortex. These findings suggest that LD is part of a novel processing stream involved in spatial orientation and learning related to somatosensory cues. J. Comp. Neurol. 507:1979–1989, 2008.

Perturbations of Respiratory Rhythm and Pattern by Disrupting Synaptic Inhibition within Pre-Bötzinger and Bötzinger Complexes

Visual Abstract The pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes are the brainstem compartments containing interneurons considered to be critically involved in generating respiratory rhythm and motor pattern in mammals. The pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes are the brainstem compartments containing interneurons considered to be critically involved in generating respiratory rhythm and motor pattern in mammals. Current models postulate that both generation of the rhythm and coordination of the inspiratory-expiratory pattern involve inhibitory synaptic interactions within and between these regions. Both regions contain glycinergic and GABAergic neurons, and rhythmically active neurons in these regions receive appropriately coordinated phasic inhibition necessary for generation of the normal three-phase respiratory pattern. However, recent experiments attempting to disrupt glycinergic and GABAergic postsynaptic inhibition in the pre-BötC and BötC in adult rats in vivo have questioned the critical role of synaptic inhibition in these regions, as well as the importance of the BötC, which contradicts previous physiological and pharmacological studies. To further evaluate the roles of synaptic inhibition and the BötC, we bilaterally microinjected the GABAA receptor antagonist gabazine and glycinergic receptor antagonist strychnine into the pre-BötC or BötC in anesthetized adult rats in vivo and in perfused in situ brainstem–spinal cord preparations from juvenile rats. Muscimol was microinjected to suppress neuronal activity in the pre-BötC or BötC. In both preparations, disrupting inhibition within pre-BötC or BötC caused major site-specific perturbations of the rhythm and disrupted the three-phase motor pattern, in some experiments terminating rhythmic motor output. Suppressing BötC activity also potently disturbed the rhythm and motor pattern. We conclude that inhibitory circuit interactions within and between the pre-BötC and BötC critically regulate rhythmogenesis and are required for normal respiratory motor pattern generation.

The Impact of a Corticotectal Impulse on the Awake Superior Colliculus

Corticotectal (CTect) neurons of layer 5 are large and prominent elements of mammalian visual cortex, with thick apical dendrites that ascend to layer 1, “intrinsically bursting” membrane properties, and fast-conducting descending axons that terminate in multiple subcortical domains. These neurons comprise a major output pathway of primary visual cortex, but virtually nothing is known about the synaptic influence of single CTect impulses on the superior colliculus (SC). Here, we examine the distribution of monosynaptic currents generated in the superficial SC by spontaneous impulses of single CTect neurons. We do this by recording the spikes of CTect neurons and the field potentials that they generate through the depths of the SC. Methods of spike-triggered averaging and current source density analysis are then applied to these data. We show, in fully awake rabbits, that single CTect impulses generate potent, fast-rising monosynaptic currents in the SC similar to those generated in sensory cortex by specific thalamic afferents. These currents are focal in depth, precisely retinotopic, and highly dependent on the conduction velocity of the CTect axon. Moreover, we show that CTect synapses, like thalamocortical synapses, suffer a chronic state of depression in awake subjects that is modulated by preceding interspike interval. However, CTect neurons generated few “bursts,” and postsynaptic responses in the SC were not significantly influenced by a shift from alert to an inattentive state (indicated by hippocampal EEG). Together, our results suggest that single CTect neurons may resemble thalamocortical neurons in their ability to serve as potent “drivers” of postsynaptic targets.

Neuromodulation of Whisking Related Neural Activity in Superior Colliculus

The superior colliculus is part of a broader neural network that can decode whisker movements in air and on objects, which is a strategy used by behaving rats to sense the environment. The intermediate layers of the superior colliculus receive whisker-related excitatory afferents from the trigeminal complex and barrel cortex, inhibitory afferents from extrinsic and intrinsic sources, and neuromodulatory afferents from cholinergic and monoaminergic nuclei. However, it is not well known how these inputs regulate whisker-related activity in the superior colliculus. We found that barrel cortex afferents drive the superior colliculus during the middle portion of the rising phase of the whisker movement protraction elicited by artificial (fictive) whisking in anesthetized rats. In addition, both spontaneous and whisker-related neural activities in the superior colliculus are under strong inhibitory and neuromodulator control. Cholinergic stimulation activates the superior colliculus by increasing spontaneous firing and, in some cells, whisker-evoked responses. Monoaminergic stimulation has the opposite effects. The actions of neuromodulator and inhibitory afferents may be the basis of the different firing rates and sensory responsiveness observed in the superior colliculus of behaving animals during distinct behavioral states.

Superior colliculus cells sensitive to active touch and texture during whisking

Rats sense the environment through rhythmic vibrissa protractions, called active whisking, which can be simulated in anesthetized rats by electrically stimulating the facial motor nerve. Using this method, we investigated barrel cortex field potential and superior colliculus single-unit responses during passive touch, whisking movement, active touch, and texture discrimination. Similar to passive touch, whisking movement is signaled during the onset of the whisker protraction by short-latency responses in barrel cortex that drive corticotectal responses in superior colliculus, and all these responses show robust adaptation with increases in whisking frequency. Active touch and texture are signaled by longer latency responses, first in superior colliculus during the rising phase of the protraction, likely driven by trigeminotectal inputs, and later in barrel cortex by the falling phase of the protraction. Thus, superior colliculus is part of a broader vibrissa neural network that can decode whisking movement, active touch, and texture.

Interdisciplinary approaches of transcranial magnetic stimulation applied to a respiratory neuronal circuitry model

Respiratory related diseases associated with the neuronal control of breathing represent life-threatening issues and to date, no effective therapeutics are available to enhance the impaired function. The aim of this study was to determine whether a preclinical respiratory model could be used for further studies to develop a non-invasive therapeutic tool applied to rat diaphragmatic neuronal circuitry. Transcranial magnetic stimulation (TMS) was performed on adult male Sprague-Dawley rats using a human figure-of-eight coil. The largest diaphragmatic motor evoked potentials (MEPdia) were recorded when the center of the coil was positioned 6 mm caudal from Bregma, involving a stimulation of respiratory supraspinal pathways. Magnetic shielding of the coil with mu metal reduced magnetic field intensities and improved focality with increased motor threshold and lower amplitude recruitment curve. Moreover, transynaptic neuroanatomical tracing with pseudorabies virus (applied to the diaphragm) suggest that connections exist between the motor cortex, the periaqueductal grey cell regions, several brainstem neurons and spinal phrenic motoneurons (distributed in the C3-4 spinal cord). These results reveal the anatomical substrate through which supraspinal stimulation can convey descending action potential volleys to the spinal motoneurons (directly or indirectly). We conclude that MEPdia following a single pulse of TMS can be successfully recorded in the rat and may be used in the assessment of respiratory supraspinal plasticity. Supraspinal non-invasive stimulations aimed to neuromodulate respiratory circuitry will enable new avenues of research into neuroplasticity and the development of therapies for respiratory dysfunction associated with neural injury and disease (e.g. spinal cord injury, amyotrophic lateral sclerosis).

Modulation of artificial whisking related signals in barrel cortex

Rats use rhythmic whisker movements, called active whisking, to sense the environment, which include whisker protractions followed by retractions at various frequencies. Using a proxy of active whisking in anesthetized rats, called artificial whisking, which is induced by electrically stimulating the facial motor nerve, we characterized the neural responses evoked in the barrel cortex by whisking in air (without contact) and on a surface (with contact). Neural responses were compared between distinct network states consisting of cortical deactivation (synchronized slow oscillations) and activation (desynchronized state) produced by neuromodulation (cholinergic or noradrenergic stimulation in neocortex or thalamus). Here we show that population responses in the barrel cortex consist of a robust signal driven by the onset of the whisker protraction followed by a whisking retraction signal that emerges during low frequency whisking on a surface. The whisking movement onset signal is suppressed by increasing whisking frequency, is controlled by cortical synaptic inhibition, is suppressed during cortical activation states, is little affected by whisking on a surface, and is ubiquitous in ventroposterior medial (VPM) thalamus, barrel cortex, and superior colliculus. The whisking retraction signal codes the duration of the preceding whisker protraction, is present in thalamocortical networks but not in superior colliculus, and is robust during cortical activation; a state associated with natural exploratory whisking. The expression of different whisking signals in forebrain and midbrain may define the sensory processing abilities of those sensorimotor circuits. Whisking related signals in the barrel cortex are controlled by network states that are set by neuromodulators.

Enhancing neural activity to drive respiratory plasticity following cervical spinal cord injury

Cervical spinal cord injury (SCI) results in permanent life-altering sensorimotor deficits, among which impaired breathing is one of the most devastating and life-threatening. While clinical and experimental research has revealed that some spontaneous respiratory improvement (functional plasticity) can occur post-SCI, the extent of the recovery is limited and significant deficits persist. Thus, increasing effort is being made to develop therapies that harness and enhance this neuroplastic potential to optimize long-term recovery of breathing in injured individuals. One strategy with demonstrated therapeutic potential is the use of treatments that increase neural and muscular activity (e.g. locomotor training, neural and muscular stimulation) and promote plasticity. With a focus on respiratory function post-SCI, this review will discuss advances in the use of neural interfacing strategies and activity-based treatments, and highlights some recent results from our own research.