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Biomedical subjects

Michael Brecht

Publications and source records attributed to Michael Brecht.

At least 19 recordsLinked to original sources
PubMed2006

Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development.

Sensory experience is necessary for normal cortical development. This has been shown by sensory deprivation and pharmacological perturbation of the cortex. Because these manipulations affect the cortical network as a whole, the role of postsynaptic cellular properties during experience-dependent development is unclear. Here we addressed the developmental role of somatodendritic excitability, which enables postsynaptic spike timing-dependent forms of plasticity, in rat somatosensory cortex. We used short interfering RNA (siRNA)-based knockdown of Na+ channels to suppress the somatodendritic excitability of small numbers of layer 2/3 pyramidal neurons in the barrel cortex, without altering the ascending sensory pathway. In vivo recordings from siRNA-expressing cells revealed that this manipulation interfered with the normal developmental strengthening of sensory responses. The sensory responsiveness of neighboring cortical neurons was unchanged, indicating that the cortical network was unchanged. We conclude that somatodendritic excitability of the postsynaptic neuron is needed for the regulation of synaptic strength in the developing sensory cortex.

Animals↗
PubMed2006

Whole-cell recordings in freely moving rats.

Intracellular recording, which allows direct measurement of the membrane potential and currents of individual neurons, requires a very mechanically stable preparation and has thus been limited to in vitro and head-immobilized in vivo experiments. This restriction constitutes a major obstacle for linking cellular and synaptic physiology with animal behavior. To overcome this limitation we have developed a method for performing whole-cell recordings in freely moving rats. We constructed a miniature head-mountable recording device, with mechanical stabilization achieved by anchoring the recording pipette rigidly in place after the whole-cell configuration is established. We obtain long-duration recordings (mean of approximately 20 min, maximum 60 min) in freely moving animals that are remarkably insensitive to mechanical disturbances, then reconstruct the anatomy of the recorded cells. This head-anchored whole-cell recording technique will enable a wide range of new studies involving detailed measurement and manipulation of the physiological properties of identified cells during natural behaviors.

Animals↗
PubMed2006

Cellular mechanisms of motor control in the vibrissal system.

In this article we discuss the experimental advantages that the vibrissal motor system offers for analysis of motor control and the specializations of this system related to the unique characteristics of whisker movements. Whisker movements are often rhythmic, fast, and bilateral. Movements of individual whiskers have simple characteristics, whereas, movements of the entire vibrissae array are complex and sophisticated. In the last few years, powerful methods for high precision tracking of whisker movements have become available. The whisker musculature is arranged to permit forward movements of individual whiskers and consists-depending on the species-mainly or exclusively of fast contracting, fast fatigable muscle fibers. Whisker motor neurons are located in the lateral facial nucleus and their cellular properties might contribute to the rhythmicity of whisking. Numerous structures provide input to the lateral facial nucleus, the most mysterious and important one being the putative central pattern generator (CPG). Although recent studies identified candidate structures for the CPG, the precise identity and the functional organization of this structure remains uncertain. The vibrissa motor cortex (VMC) is the largest motor representation in the rodent brain, and recent work has clarified its localization, subdivisions, cytoarchitectonics, and connectivity. Single-cell stimulation experiments in VMC allow determining the cellular basis of cortical motor control with unprecedented precision. The functional significance of whisker movements remains to be determined.

Animals↗
PubMed2006

Cortical commands in active touch.

The neocortex is an enormous network of extensively interconnected neurons. It has become clear that the computations performed by individual cortical neurons will critically depend on the quantitative composition of cortical activity. Here we discuss quantitative aspects of cortical activity and modes of cortical processing in the context of rodent active touch. Through in vivo whole-cell recordings one observes widespread subthreshold and very sparse evoked action potential (AP) activity in the somatosensory cortex both for passive whisker deflection in anaesthetized animals and during active whisker movements in awake animals. Neurons of the somatosensory cortex become either suppressed during whisking or activated by an efference copy of whisker movement signal that depolarize cells at certain phases of the whisking cycle. To probe the read out of cortical motor commands we applied intracellular stimulation in rat whisker motor cortex. We find that APs in individual cortical neurons can evoke long sequences of small whisker movements. The capacity of an individual neuron to evoke movements is most astonishing given the large number of neurons in whisker motor cortex. Thus, few cortical APs may suffice to control motor behaviour and such APs can be translated into action with the utmost precision. We conclude that there is very widespread subthreshold cortical activity and very sparse, highly specific cortical AP activity.

Action Potentials↗
PubMed2005

Map plasticity in somatosensory cortex.

Sensory maps in neocortex are adaptively altered to reflect recent experience and learning. In somatosensory cortex, distinct patterns of sensory use or disuse elicit multiple, functionally distinct forms of map plasticity. Diverse approaches-genetics, synaptic and in vivo physiology, optical imaging, and ultrastructural analysis-suggest a distributed model in which plasticity occurs at multiple sites in the cortical circuit with multiple cellular/synaptic mechanisms and multiple likely learning rules for plasticity. This view contrasts with the classical model in which the map plasticity reflects a single Hebbian process acting at a small set of cortical synapses.

Animals↗
PubMed2005

Monosynaptic pathway from rat vibrissa motor cortex to facial motor neurons revealed by lentivirus-based axonal tracing.

The mammalian motor cortex typically innervates motor neurons indirectly via oligosynaptic pathways. However, evolution of skilled digit movements in humans, apes, and some monkey species is associated with the emergence of abundant monosynaptic cortical projections onto spinal motor neurons innervating distal limb muscles. Rats perform skilled movements with their whiskers, and we examined the possibility that the rat vibrissa motor cortex (VMC) projects monosynaptically onto facial motor neurons controlling the whisker movements. First, single injections of lentiviruses to VMC sites identified by intracortical microstimulations were used to label a distinct subpopulation of VMC axons or presynaptic terminals by expression of enhanced green fluorescent protein (GFP) or GFP-tagged synaptophysin, respectively. Four weeks after the injections, GFP and synaptophysin-GFP labeling of axons and putative presynaptic terminals was detected in the lateral portion of the facial nucleus (FN), in close proximity to motor neurons identified morphologically and by axonal back-labeling from the whisker follicles. The VMC projections were detected bilaterally, with threefold larger density of labeling in the contralateral FN. Next, multiple VMC injections were used to label a large portion of VMC axons, resulting in overall denser but still laterally restricted FN labeling. Ultrastructural analysis of the GFP-labeled VMC axons confirmed the existence of synaptic contacts onto dendrites and somata of FN motor neurons. These findings provide anatomical demonstration of monosynaptic VMC-to-FN pathway in the rat and show that lentivirus-based expression of GFP and GFP-tagged presynaptic proteins can be used as a high-resolution neuroanatomical tracing method.

Animals↗
PubMed2005

TbMP42, a protein component of the RNA editing complex in African trypanosomes, has endo-exoribonuclease activity.

RNA editing in trypanosomatids is catalyzed by a high molecular mass RNP complex, which is only partially characterized. TbMP42 is a 42 kDa protein of unknown function that copurifies with the editing complex. The polypeptide is characterized by two Zn fingers and a potential barrel structure/OB-fold at its C terminus. Using recombinant TbMP42, we show that the protein can bind to dsRNA and dsDNA but fails to recognize DNA/RNA hybrids. rTbMP42 degrades ssRNA by a 3' to 5' exoribonuclease activity. In addition, rTbMP42 has endoribonuclease activity, which preferentially hydrolyzes non-base-paired uridylate-containing sequences. Gene silencing of TbMP42 inhibits cell growth and is ultimately lethal to the parasite. Mitochondrial extracts from TbMP42-minus trypanosomes have only residual RNA editing activity and strongly reduced endo-exoribonuclease activity. However, all three activities can be restored by the addition of rTbMP42. Together, the data suggest that TbMP42 contributes both endo- and exoribonuclease activity to the editing reaction cycle.

Animals↗
PubMed2004

Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo.

It is becoming increasingly clear that single cortical neurons encode complex and behaviorally relevant signals, but efficient means to study gene functions in small networks and single neurons in vivo are still lacking. Here, we establish a method for genetic manipulation and subsequent phenotypic analysis of individual cortical neurons in vivo. First, lentiviral vectors are used for neuron-specific gene delivery from alpha-calcium/calmodulin-dependent protein kinase II or Synapsin I promoters, optionally in combination with gene knockdown by means of U6 promoter-driven expression of short-interfering RNAs. Second, the phenotypic analysis at the level of single cortical cells is carried out by using two-photon microscopy-based techniques: high-resolution two-photon time-lapse imaging is used to monitor structural dynamics of dendritic spines and axonal projections, whereas cellular response properties are analyzed electrophysiologically by two-photon microscopy directed whole-cell recordings. This approach is ideally suited for analysis of gene functions in individual neurons in the intact brain.

Animals↗
PubMed2004

Organization of rat vibrissa motor cortex and adjacent areas according to cytoarchitectonics, microstimulation, and intracellular stimulation of identified cells.

The relationship between motor maps and cytoarchitectonic subdivisions in rat frontal cortex is not well understood. We use cytoarchitectonic analysis of microstimulation sites and intracellular stimulation of identified cells to develop a cell-based partitioning scheme of rat vibrissa motor cortex and adjacent areas. The results suggest that rat primary motor cortex (M1) is composed of three cytoarchitectonic areas, the agranular medial field (AGm), the agranular lateral field (AG1), and the cingulate area 1 (Cg1), each of which represents movements of different body parts. Vibrissa motor cortex corresponds entirely and for the most part exclusively to AGm. In area AG1 body/head movements can be evoked. In posterior area Cg1 periocular/eye movements and in anterior area Cg1 nose movements can be evoked. In all of these areas stimulation thresholds are very low, and together they form a complete representation of the rat's body surface. A strong myelinization and an expanded layer 5 characterize area AGm. We suggest that both the strong myelinization and the expanded layer 5 of area AGm may represent cytoarchitectonic specializations related to control of high-speed whisking behavior.

Action Potentials↗
PubMed2004

Retraction.

Explore the source record for details and available documents.

Retraction Notice↗
PubMed2004

RETRACTED: Synaptic changes in layer 2/3 underlying map plasticity of developing barrel cortex.

The functional and anatomical rearrangements of cortical sensory maps accompanying changes in experience are not well understood. We examined in vivo and in vitro how the sensory map and underlying synaptic connectivity of the developing rat barrel cortex are altered when the sensory input to the cortex is partially deprived. In the nondeprived cortex, both the sensory responses and synaptic connectivity between columns were strengthened through an increase in the synaptic connection probability between L2/3 pyramids in adjacent columns. This was accompanied by a selective growth of L2/3pyramid axonal arbors between spared columns. In contrast, deprived and nondeprived cortical columns became weakly connected in their L2/3 pyramid connections.

Action Potentials↗
PubMed2004

Fiber types of the intrinsic whisker muscle and whisking behavior.

Some rodent species show rhythmic bouts of vibrissal protractions and retractions, referred to as whisking, that are among the fastest movements performed by mammals. To better understand the muscular basis of whisking, we compared (1) whisker movements of two whisking species (mouse, rat) and a non-whisking species (guinea pig), (2) the muscle fiber composition of intrinsic whisker muscles of whisking and a non-whisking species, and (3) the muscle fiber composition of intrinsic whisker muscles and of selected skeletal muscles. Using high-speed videography, we found that mice, rats, and guinea pigs can generate fast and large-amplitude whisker movements. Guinea pigs do not show bouts of fast, strictly rhythmic whisker movements, and the average speed of their whisker movements is much lower than in mice and rats. Analysis of mRNA expression of myosin heavy chain isoforms, myofibrillar ATPase staining, and antibody labeling indicate that in all three species intrinsic whisker muscles are composed predominantly of type 2B muscle fibers. Intrinsic whisker muscles of mice consisted of type 2B (> or =90%) and type 2D fibers. In rats we observed, in addition to type 2B/2D fibers, approximately 10% of slow type 1 fibers, and in guinea pigs we observed approximately 3% of slow type 1 fibers and 20% of type 2A fibers. Type 2B fibers have high levels of anaerobic glycolytic enzymes providing a rapid source of ATP and high maximum velocity of contraction but are less fatigue resistant than other muscle fiber types. The high percentage of type 2B fibers distinguishes the intrinsic whisker musculature from skeletal muscles and may have evolved for fast scanning of the sensory environment.

Adenosine Triphosphatases↗
PubMed2004

Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex.

Neuronal activity in the motor cortex is understood to be correlated with movements, but the impact of action potentials (APs) in single cortical neurons on the generation of movement has not been fully determined. Here we show that trains of APs in single pyramidal cells of rat motor cortex can evoke long sequences of small whisker movements. For layer-5 pyramids, we find that evoked rhythmic movements have a constant phase relative to the AP train, indicating that single layer-5 pyramids can reset the rhythm of whisker movements. Action potentials evoked in layer-6 pyramids can generate bursts of rhythmic whisking, with a variable phase of movements relative to the AP train. An increasing number of APs decreases the latency to onset of movement, whereas AP frequency determines movement direction and amplitude. We find that the efficacy of cortical APs in evoking whisker movements is not dependent on background cortical activity and is greatly enhanced in waking rats. We conclude that in vibrissae motor cortex sparse AP activity can evoke movements.

Action Potentials↗
PubMed2004

Amplitude and direction of saccadic eye movements depend on the synchronicity of collicular population activity.

Synchronization of neuronal discharges has been observed in numerous brain structures, but opinions diverge regarding its significance in neuronal processing. Here we investigate whether the motion vectors of saccadic eye movements evoked by electrical multisite stimulation of the cat superior colliculus (SC) are influenced by varying the degree of synchrony between the stimulus trains. With synchronous activation of SC sites, the vectors of the resulting saccades correspond approximately to the averages of the vectors of saccades evoked from each site alone. In contrast, when the pulses of trains applied to the different sites are temporally offset by as little as 5-10 ms, the vectors of the resulting saccades come close to the sum of the individual vectors. Thus saccade vectors depend not only on the site and amplitude of collicular activation but also on the precise temporal relations among the respective spike trains. These data indicate that networks within or downstream from the SC discriminate with high temporal resolution between synchronous and asynchronous population responses. This supports the hypothesis that information is encoded not only in the rate of neuronal responses but also in the precise temporal relations between discharges.

Action Potentials↗
PubMed2004

Sub- and suprathreshold receptive field properties of pyramidal neurones in layers 5A and 5B of rat somatosensory barrel cortex.

Layer 5 (L5) pyramidal neurones constitute a major sub- and intracortical output of the somatosensory cortex. This layer 5 is segregated into layers 5A and 5B which receive and distribute relatively independent afferent and efferent pathways. We performed in vivo whole-cell recordings from L5 neurones of the somatosensory (barrel) cortex of urethane-anaesthetized rats (aged 27-31 days). By delivering 6 deg single whisker deflections, whisker pad receptive fields were mapped for 16 L5A and 11 L5B neurones located below the layer 4 whisker-barrels. Average resting membrane potentials were -75.6 +/- 1.1 mV, and spontaneous action potential (AP) rates were 0.54 +/- 0.14 APs s(-1). Principal whisker (PW) evoked responses were similar in L5A and L5B neurones, with an average 5.0 +/- 0.6 mV postsynaptic potential (PSP) and 0.12 +/- 0.03 APs per stimulus. The layer 5A sub- and suprathreshold receptive fields (RFs) were more confined to the principle whisker than those of layer 5B. The basal dendritic arbors of layer 5A and 5B cells were located below both layer 4 barrels and septa, and the cell bodies were biased towards the barrel walls. Responses in both L5A and L5B developed slowly, with onset latencies of 10.1 +/- 0.5 ms and peak latencies of 33.9 +/- 3.3 ms. Contralateral multi-whisker stimulation evoked PSPs similar in amplitude to those of PW deflections; whereas, ipsilateral stimulation evoked smaller and longer latency PSPs. We conclude that in L5 a whisker deflection is represented in two ways: focally by L5A pyramids and more diffusely by L5B pyramids as a result of combining different inputs from lemniscal and paralemniscal pathways. The relevant output evoked by a whisker deflection could be the ensemble activity in the anatomically defined cortical modules associated with a single or a few barrel-columns.

Afferent Pathways↗