Stimulation Of Vibrissae Research Articles

High-resolution awake mouse fMRI at 14 Tesla.

High-resolution awake mouse fMRI remains challenging despite extensive efforts to address motion-induced artifacts and stress. This study introduces an implantable radiofrequency (RF) surface coil design that minimizes image distortion caused by the air/tissue interface of mouse brains while simultaneously serving as a headpost for fixation during scanning. Furthermore, this study provides a thorough acclimation method used to accustom animals to the MRI environment minimizing motion induced artifacts. Using a 14T scanner, high-resolution fMRI enabled brain-wide functional mapping of visual and vibrissa stimulation at 100×100×200μm resolution with a 2s per frame sampling rate. Besides activated ascending visual and vibrissa pathways, robust BOLD responses were detected in the anterior cingulate cortex upon visual stimulation and spread through the ventral retrosplenial area (VRA) with vibrissa air-puff stimulation, demonstrating higher-order sensory processing in association cortices of awake mice. In particular, the rapid hemodynamic responses in VRA upon vibrissa stimulation showed a strong correlation with the hippocampus, thalamus, and prefrontal cortical areas. Cross-correlation analysis with designated VRA responses revealed early positive BOLD signals at the contralateral barrel cortex (BC) occurring 2 seconds prior to the air-puff in awake mice with repetitive stimulation, which was not detected using a randomized stimulation paradigm. This early BC activation indicated a learned anticipation through the vibrissa system and association cortices in awake mice under continuous training of repetitive air-puff stimulation. This work establishes a high-resolution awake mouse fMRI platform, enabling brain-wide functional mapping of sensory signal processing in higher association cortical areas.

Conditioning and pseudoconditioning differently change intrinsic excitability of inhibitory interneurons in the neocortex.

Many studies indicate a broad role of various classes of GABAergic interneurons in the processes related to learning. However, little is known about how the learning process affects intrinsic excitability of specific classes of interneurons in the neocortex. To determine this, we employed a simple model of conditional learning in mice where vibrissae stimulation was used as a conditioned stimulus and a tail shock as an unconditioned one. In vitro whole-cell patch-clamp recordings showed an increase in intrinsic excitability of low-threshold spiking somatostatin-expressing interneurons (SST-INs) in layer 4 (L4) of the somatosensory (barrel) cortex after the conditioning paradigm. In contrast, pseudoconditioning reduced intrinsic excitability of SST-LTS, parvalbumin-expressing interneurons (PV-INs), and vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) with accommodating pattern in L4 of the barrel cortex. In general, increased intrinsic excitability was accompanied by narrowing of action potentials (APs), whereas decreased intrinsic excitability coincided with AP broadening. Altogether, these results show that both conditioning and pseudoconditioning lead to plastic changes in intrinsic excitability of GABAergic interneurons in a cell-specific manner. In this way, changes in intrinsic excitability can be perceived as a common mechanism of learning-induced plasticity in the GABAergic system.

Impact of somatostatin interneurons on interactions between barrels in plasticity induced by whisker deprivation

The activity of inhibitory interneurons has a profound role in shaping cortical plasticity. Somatostatin-expressing interneurons (SOM-INs) are involved in several aspects of experience-dependent cortical rewiring. We addressed the question of the barrel cortex SOM-IN engagement in plasticity formation induced by sensory deprivation in adult mice (2–3 months old). We used a spared vibrissa paradigm, resulting in a massive sensory map reorganization. Using chemogenetic manipulation, the activity of barrel cortex SOM-INs was blocked or activated by continuous clozapine N-oxide (CNO) administration during one-week-long deprivation. To visualize the deprivation-induced plasticity, [14C]-2-deoxyglucose mapping of cortical functional representation of the spared whisker was performed at the end of the deprivation. The plasticity was manifested as an extension of cortical activation in response to spared vibrissae stimulation. We found that SOM-IN inhibition in the cortical column of the spared whisker did not influence the areal extent of the cortex activated by the spared whisker. However, blocking the activity of SOM-INs in the deprived column, adjacent to the spared one, decreased the plasticity of the spared whisker representation. SOM-IN activation did not affect plasticity. These data show that SOM-IN activity is part of cortical circuitry that affects interbarrel interactions underlying deprivation-induced plasticity in adult mice.

Simultaneous Two-Photon Voltage or Calcium Imaging and Multi-Channel Local Field Potential Recordings in Barrel Cortex of Awake and Anesthetized Mice.

Neuronal population activity, both spontaneous and sensory-evoked, generates propagating waves in cortex. However, high spatiotemporal-resolution mapping of these waves is difficult as calcium imaging, the work horse of current imaging, does not reveal subthreshold activity. Here, we present a platform combining voltage or calcium two-photon imaging with multi-channel local field potential (LFP) recordings in different layers of the barrel cortex from anesthetized and awake head-restrained mice. A chronic cranial window with access port allows injecting a viral vector expressing GCaMP6f or the voltage-sensitive dye (VSD) ANNINE-6plus, as well as entering the brain with a multi-channel neural probe. We present both average spontaneous activity and average evoked signals in response to multi-whisker air-puff stimulations. Time domain analysis shows the dependence of the evoked responses on the cortical layer and on the state of the animal, here separated into anesthetized, awake but resting, and running. The simultaneous data acquisition allows to compare the average membrane depolarization measured with ANNINE-6plus with the amplitude and shape of the LFP recordings. The calcium imaging data connects these data sets to the large existing database of this important second messenger. Interestingly, in the calcium imaging data, we found a few cells which showed a decrease in calcium concentration in response to vibrissa stimulation in awake mice. This system offers a multimodal technique to study the spatiotemporal dynamics of neuronal signals through a 3D architecture in vivo. It will provide novel insights on sensory coding, closing the gap between electrical and optical recordings.

Delayed Treatment with Human Dental Pulp Stem Cells Accelerates Functional Recovery and Modifies Responses of Peri-Infarct Astrocytes Following Photothrombotic Stroke in Rats

Dental pulp contains multipotent mesenchymal stem cells that improve outcomes when administered early after temporary middle cerebral artery occlusion in rats. To further assess the therapeutic potential of these cells, we tested whether functional recovery following stroke induced by photothrombosis could be modified by a delayed treatment that was initiated after the infarct attained maximal volume. Photothrombosis induces permanent focal ischemia resulting in tissue changes that better reflect key aspects of the many human strokes in which early restoration of blood flow does not occur. Human dental pulp stem cells (approximately 400 × 103 viable cells) or vehicle were injected into the infarct and adjacent brain tissue of Sprague-Dawley rats at 3 days after the induction of unilateral photothrombotic stroke in the sensorimotor cortex. Forepaw function was tested up to 28 days after stroke. Cellular changes in peri-infarct tissue at 28 days were assessed using immunohistochemistry. Rats treated with the stem cells showed faster recovery compared with vehicle-treated animals in a test of forelimb placing in response to vibrissae stimulation and in first attempt success in a skilled forelimb reaching test. Total success in the skilled reaching test and forepaw use during exploration in a Perspex cylinder were not significantly different between the 2 groups. At 28 days after stroke, rats treated with the stem cells showed decreased immunolabeling for glial fibrillary acidic protein in tissue up to 1 mm from the infarct, suggesting decreased reactive astrogliosis. Synaptophysin, a marker of synapses, and collagen IV, a marker of capillaries, were not significantly altered at this time by the stem-cell treatment. These results indicate that dental pulp stem cells can accelerate recovery without modifying initial infarct formation. Decreases in reactive astrogliosis in peri-infarct tissue could have contributed to the change by promoting adaptive responses in neighboring neurons.

Heterogeneity of Sensory-Induced Astrocytic Ca2+ Dynamics During Functional Hyperemia.

Astrocytic Ca2+ fluctuations associated with functional hyperemia have typically been measured from large cellular compartments such as the soma, the whole arbor and the endfoot. The most prominent Ca2+ event is a large magnitude, delayed signal that follows vasodilation. However, previous work has provided little information about the spatio-temporal properties of such Ca2+ transients or their heterogeneity. Here, using an awake, in vivo two-photon fluorescence-imaging model, we performed detailed profiling of delayed astrocytic Ca2+ signals across astrocytes or within individual astrocyte compartments using small regions of interest next to penetrating arterioles and capillaries along with vasomotor responses to vibrissae stimulation. We demonstrated that while a 5-s air puff that stimulates all whiskers predominantly generated reproducible functional hyperemia in the presence or absence of astrocytic Ca2+ changes, whisker stimulation inconsistently produced astrocytic Ca2+ responses. More importantly, these Ca2+ responses were heterogeneous among subcellular structures of the astrocyte and across different astrocytes that resided within the same field of view. Furthermore, we found that whisker stimulation induced discrete Ca2+ “hot spots” that spread regionally within the endfoot. These data reveal that astrocytic Ca2+ dynamics associated with the microvasculature are more complex than previously thought, and highlight the importance of considering the heterogeneity of astrocytic Ca2+ activity to fully understanding neurovascular coupling.

Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain

BackgroundStimulation of the occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the ‘trigeminocervical complex’ (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in the spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad.MethodsAdult male Wistar rats were used. Neuronal recordings were obtained in laminae II-IV in the TCC in control, sham and infraorbital chronic constriction injury (CCI-IoN) animals. The GON was isolated and electrically stimulated. Responses to the stimulation of vibrissae by brief air pulses were analyzed before and after GON stimulation. In order to understand the role of the neurotransmitters involved, specific receptor blockers of NMDA (AP-5), GABAA (bicuculline, Bic) and Glycine (strychnine, Str) were applied locally.ResultsGON stimulation produced a facilitation of the response to light facial mechanical stimuli in controls, and an inhibition in CCI-IoN cases. AP-5 reduced responses to GON and vibrissal stimulation and blocked the facilitation of GON on vibrissal responses found in controls. The application of Bic or Str significantly reduced the facilitatory effect of GON stimulation on the response to vibrissal stimulation in controls. However, the opposite effect was found when GABAergic or Glycinergic transmission was prevented in CCI-IoN cases.ConclusionsGON stimulation modulates the responses of TCC neurons to light mechanical input from the face in opposite directions in controls and under CCI-IoN. This modulation is mediated by GABAergic and Glycinergic mechanisms. These results will help to elucidate the neural mechanisms underlying the effectiveness of nerve stimulation in controlling painful craniofacial disorders, and may be instrumental in identifying new therapeutic targets for their prevention and treatment.

Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation

Astrocytes possess many of the same signalling molecules as neurons. However, the role of astrocytes in information processing, if any, is unknown. Using electrophysiological and imaging methods, we report the first evidence that astrocytes modulate neuronal sensory inhibition in the rodent thalamus.We found that mGlu2 receptor activity reduces inhibitory transmission from the thalamic reticular nucleus to the somatosensory ventrobasal thalamus (VB): mIPSC frequencies in VB slices were reduced by the Group II mGlu receptor agonist LY354740, an effect potentiated by mGlu2 positive allosteric modulator (PAM) LY487379 co-application (30 nM LY354740: 10.0 ± 1.6% reduction; 30 nM LY354740 & 30 μM LY487379: 34.6 ± 5.2% reduction).We then showed activation of mGlu2 receptors on astrocytes: astrocytic intracellular calcium levels were elevated by the Group II agonist, which were further potentiated upon mGlu2 PAM co-application (300 nM LY354740: ratio amplitude 0.016 ± 0.002; 300 nM LY354740 & 30 μM LY487379: ratio amplitude 0.035 ± 0.003).We then demonstrated mGlu2-dependent astrocytic disinhibition of VB neurons in vivo: VB neuronal responses to vibrissae stimulation trains were disinhibited by the Group II agonist and the mGlu2 PAM (LY354740: 156 ± 12% of control; LY487379: 144 ± 10% of control). Presence of the glial inhibitor fluorocitrate abolished the mGlu2 PAM effect (91 ± 5% of control), suggesting the mGlu2 component to the Group II effect can be attributed to activation of mGlu2 receptors localised on astrocytic processes within the VB.Gating of thalamocortical function via astrocyte activation represents a novel sensory processing mechanism. As this thalamocortical circuitry is important in discriminative processes, this demonstrates the importance of astrocytes in synaptic processes underlying attention and cognition.

Feedforward motor information enhances somatosensory responses and sharpens angular tuning of rat S1 barrel cortex neurons

The primary vibrissae motor cortex (vM1) is responsible for generating whisking movements. In parallel, vM1 also sends information directly to the sensory barrel cortex (vS1). In this study, we investigated the effects of vM1 activation on processing of vibrissae sensory information in vS1 of the rat. To dissociate the vibrissae sensory-motor loop, we optogenetically activated vM1 and independently passively stimulated principal vibrissae. Optogenetic activation of vM1 supra-linearly amplified the response of vS1 neurons to passive vibrissa stimulation in all cortical layers measured. Maximal amplification occurred when onset of vM1 optogenetic activation preceded vibrissa stimulation by 20 ms. In addition to amplification, vM1 activation also sharpened angular tuning of vS1 neurons in all cortical layers measured. Our findings indicated that in addition to output motor signals, vM1 also sends preparatory signals to vS1 that serve to amplify and sharpen the response of neurons in the barrel cortex to incoming sensory input signals.

Precision mapping of the vibrissa representation within murine primary somatosensory cortex.

The ability to form an accurate map of sensory input to the brain is an essential aspect of interpreting functional brain signals. Here, we consider the somatotopic map of vibrissa-based touch in the primary somatosensory (vS1) cortex of mice. The vibrissae are represented by a Manhattan-like grid of columnar structures that are separated by inter-digitating septa. The development, dynamics and plasticity of this organization is widely used as a model system. Yet, the exact anatomical position of this organization within the vS1 cortex varies between individual mice. Targeting of a particular column in vivo therefore requires prior mapping of the activated cortical region, for instance by imaging the evoked intrinsic optical signal (eIOS) during vibrissa stimulation. Here, we describe a procedure for constructing a complete somatotopic map of the vibrissa representation in the vS1 cortex using eIOS. This enables precise targeting of individual cortical columns. We found, using C57BL/6 mice, that although the precise location of the columnar field varies between animals, the relative spatial arrangement of the columns is highly preserved. This finding enables us to construct a canonical somatotopic map of the vibrissae in the vS1 cortex. In particular, the position of any column, in absolute anatomical coordinates, can be established with near certainty when the functional representations in the vS1 cortex for as few as two vibrissae have been mapped with eIOS.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.

Tonic Local Brain Blood Flow Control by Astrocytes Independent of Phasic Neurovascular Coupling.

According to the current model of neurovascular coupling, blood flow is controlled regionally through phasic changes in the activity of neurons and astrocytes that signal to alter arteriole diameter. Absent in this model, however, is how brain blood flow is tonically regulated independent of regional changes in activity. This is important because a large fraction of brain blood flow is required to maintain basal metabolic needs. Using two-photon fluorescence imaging combined with patch-clamp in acute rat brain slices of sensory-motor cortex, we demonstrate that reducing resting Ca(2+) in astrocytes with intracellular BAPTA causes vasoconstriction in adjacent arterioles. BAPTA-induced vasoconstriction was eliminated by a general COX blocker and the effect is mimicked by a COX-1, but not COX-2, antagonist, suggesting that astrocytes provide tonic, steady-state vasodilation by releasing prostaglandin messengers. Tonic vasodilation was insensitive to TTX, as well as a variety of synaptic and extrasynaptic receptor antagonists, indicating that the phenomenon operates largely independent of neural activity. Using in vivo two-photon fluorescence imaging of the barrel cortex in fully awake mice, we reveal that acute COX-1 inhibition reduces resting arteriole diameter but fails to affect vasodilation in response to vibrissae stimulation. Our findings demonstrate that astrocytes provide tonic regulation of arterioles using resting intracellular Ca(2+) in a manner that is independent of phasic, neuronal-evoked vasodilation. Significance statement: The brain requires both phasic and tonic regulation of its blood supply to service energy needs over various temporal windows. While many mechanisms have been described for phasic blood flow regulation, how the brain accomplishes tonic control is largely unknown. Here we describe a way in which astrocytes contribute to the management of basal brain blood flow by providing steady-state vasodilation to arterioles via resting astrocyte Ca(2+) and the continuous release of prostaglandin messengers. This phenomenon may be important for understanding the declines in basal brain blood flow that occur in aging and dementia, as well as for the interpretation of fMRI data.

Opposite Adaptive Processing of Stimulus Intensity in Two Major Nuclei of the Somatosensory Brainstem

Tactile information ascends from the brainstem to the somatosensory cortex via two major parallel pathways, lemniscal and paralemniscal. In both pathways, and throughout all processing stations, adaptation effects are evident. Although parallel processing of sensory information is not unique to this system, the distinct information carried by these adaptive pathways remains unclear. Using in vivo intracellular recordings at their divergence point (brainstem trigeminal complex) in rats, we found opposite adaptation effects in the corresponding nuclei of these two pathways. Increasing the intensity of vibrissa stimulation entailed more adaption in paralemniscal neurons, whereas it caused less adaptation in lemniscal cells. Furthermore, increasing the intensity sharpens lemniscal receptive field profile as adaptation progresses. We hypothesize that these pathways evolved to operate optimally at different dynamic ranges of sustained sensory stimulation. Accordingly, the two pathways are likely to serve different functional roles in the transmission of weak and strong inputs. Hence, our results suggest that due to the disparity in the adaptation properties of two major parallel pathways in this system, high and reliable throughput of information can be achieved at a wider range of stimulation intensities than by each pathway alone.

Correlated activation of the thalamocortical network in a simple learning paradigm

The thalamocortical loop is a key player in sensory processing. We examined the functional interactions among its elements, expressed as cross-correlations between metabolic activity of the barrel cortex, somatosensory thalamic nuclei and posterior parietal cortex, in classical conditioning. In the training stimulation of vibrissae in mice was paired with a tail shock. [14C]-2-Deoxyglucose brain mapping was performed during the first and the final sessions of conditioning (conditioned stimulus+unconditioned stimulus; CS+UCS), in groups that received only the stimulation of vibrissae (conditioned stimulus; CS-only) and in nonstimulated controls (NS). In the CS-only group, the CS evoked the correlated activity of the examined structures during the first session, but in the third session these structures did not act in a correlated manner. Conversely, in the CS+UCS condition correlations among the thalamocortical loop structures activities became stronger during the course of the training. Particularly, the posterior parietal cortex, which controls voluntary deployment of attention, together with the barrel cortex becomes involved in the network of structures with the correlated activity. The results suggest a predominant role for bottom-up processing in the somatosensory pathway at the beginning of conditioning followed by top-down processing. This is consistent with the idea that the thalamocortical loop plays a crucial role in attentional processes.

Introduction to “the behavior-analytic origins of constraint-induced movement therapy: An example of behavioral neurorehabilitation”

Introduction to “the behavior-analytic origins of constraint-induced movement therapy: An example of behavioral neurorehabilitation”

The RAT-ROTADRUM: A reaction time task depending on a continuous stream of tactile sensory information to the rat

Rats running in their natural habitat monitor the immediate environment with their micro- and macrovibrissae as if reading Braille. These sensory inputs can serve as a cue to change their ongoing motor patterns, for instance to avoid obstacles. To mimic this behavior in a laboratory setting we present a novel behavioral test design. It includes a self-controlled stimulus presentation with sensory discrimination acting as a cue to redirect motor behavior. To acquire the final paradigm, rats undergo a sequenced training protocol. Extracellular neuronal activity was recorded during task performance in the final paradigm. Together with this behavioral test box we present a flexible, easy to build and affordable modular stimulus control system.

Fluctuating and sensory-induced vasodynamics in rodent cortex extend arteriole capacity

Neural activity in the brain is followed by localized changes in blood flow and volume. We address the relative change in volume for arteriole vs. venous blood within primary vibrissa cortex of awake, head-fixed mice. Two-photon laser-scanning microscopy was used to measure spontaneous and sensory evoked changes in flow and volume at the level of single vessels. We find that arterioles exhibit slow (<1 Hz) spontaneous increases in their diameter, as well as pronounced dilation in response to both punctate and prolonged stimulation of the contralateral vibrissae. In contrast, venules dilate only in response to prolonged stimulation. We conclude that stimulation that occurs on the time scale of natural stimuli leads to a net increase in the reservoir of arteriole blood. Thus, a "bagpipe" model that highlights arteriole dilation should augment the current "balloon" model of venous distension in the interpretation of fMRI images.

Bilateral Plasticity of Vibrissae SII Representation Induced by Classical Conditioning in Mice

The somatosensory cortex in mice contains primary (SI) and secondary (SII) areas, differing in somatotopic precision, topographic organization, and function. The role of SII in somatosensory processing is still poorly understood. SII is activated bilaterally during attentional tasks and is considered to play a role in tactile memory and sensorimotor integration. We measured the plasticity of SII activation after associative learning based on classical conditioning, in which unilateral stimulation of one row of vibrissae was paired with a tail shock. The training consisted of three daily 10 min sessions, during which 40 pairings were delivered. Cortical activation driven by stimulation of vibrissae was mapped with 2-[(14)C]deoxyglucose (2DG) autoradiography 1 d after the end of conditioning. We reported previously that the conditioning procedure resulted in unilateral enlargement of 2DG-labeled cortical representation of the "trained" row of vibrissae in SI. Here, we measured the width and intensity of the labeled region in SII. We found that both measured parameters in SII increased bilaterally. The increase was observed in cortical layers II/III and IV. Apparently, plasticity in SII is not a simple reflection of changes in SI. It may be attributable to bilateral integrative role of SII, its lesser topographical specificity, and strong involvement in attentional processing.

Effects of zona incerta lesions on striatal neurochemistry and behavioral asymmetry in 6‐hydroxydopamine‐lesioned rats

Analysis of optimal sites for neurosurgical interventions in patients with Parkinson's disease (PD) suggests that significant clinical benefits may be achieved by involvement of the zona incerta (ZI). Unilateral electrolytic ZI lesions were made in intact and ipsilaterally 6-hydroxydopamine (6OHDA)-lesioned rats. Extracellular levels of glutamate, dopamine, and its metabolites in the ipsilateral striatum of awake rats were measured by using microdialysis, and tests of behavioral asymmetry were performed. In intact rats, ZI lesions had no effect on striatal extracellular glutamate or absolute levels of dopamine or metabolites, but dopamine metabolism decreased. After ZI lesions, contralateral forepaw use decreased in the forepaw adjusting steps test, but there was no change in response to vibrissa stimulation or cylinder exploration. There was no development of rotational asymmetry with amphetamine. In 6OHDA-lesioned rats, striatal extracellular glutamate levels were elevated compared with controls. ZI lesions reduced the increased levels of glutamate back to normal values. ZI lesions reduced dopamine and homovanillic acid levels and showed a trend toward a decrease in dopamine metabolism. 6OHDA-lesioned rats demonstrated the expected asymmetry of motor behaviors. After ZI lesions, ipsilateral turns following amphetamine injection were reduced, and there was a trend toward improved symmetry of forepaw use as determined with the forepaw adjusting steps test. There was no change in forepaw use with vibrissa stimulation or cylinder exploration. These data indicate that lesions of the ZI can affect striatal neurochemistry and motor behavioral asymmetry and suggest potential mechanisms by which ZI lesions may improve symptoms in PD.

Involvement of retrosplenial cortex in classical conditioning

The cingulate cortex, which comprises of two major subdivisions – anterior cingulate cortex (CG) and retrosplenial cortex (RSP), is implicated in many cognitive functions. The RSP is an important node in the systemic integration network. Studies point to its role in learning that involves spatial stimuli and navigation. Relatively little is known about its involvement in simple learning such as classical conditioning. We examined the involvement of the two cytoarchitectonic divisions, agranular and granular, of the rostral and caudal RSP in a delay conditioning, where stimulation of the facial vibrissae was paired with a tail shock. During the conditioning session the [ 14C]-2-deoxyglucose (2DG) brain mapping was performed. Effectiveness of conditioning was assessed with frequency of head movements, which decreased in the course of the conditioning. 2DG uptake in RSP and additionally in CG was examined in conditioned, pseudoconditioned and stimulated control groups. The metabolic labeling was elevated in caudal and rostral both RSP and CG in the conditioned group, but not in animals which received CS or UCS alone. Comparison between conditioned and pseudoconditioned groups showed the specific activation by associative learning in both divisions of the rostral RSP and rostral CG. Counts of c-Fos expressing nuclei confirmed activation of the rostral RSP in the CS + UCS group. These data support the concept of RSP as structure that, besides its recognized role in visuospatial learning, monitors and reacts to activity of brain systems responsible for other types of learning and, together with CG, subserve cognitive processes, with simple associative learning among them.

The computational structure of spike trains.

Neurons perform computations, and convey the results of those computations through the statistical structure of their output spike trains. Here we present a practical method, grounded in the information-theoretic analysis of prediction, for inferring a minimal representation of that structure and for characterizing its complexity. Starting from spike trains, our approach finds their causal state models (CSMs), the minimal hidden Markov models or stochastic automata capable of generating statistically identical time series. We then use these CSMs to objectively quantify both the generalizable structure and the idiosyncratic randomness of the spike train. Specifically, we show that the expected algorithmic information content (the information needed to describe the spike train exactly) can be split into three parts describing (1) the time-invariant structure (complexity) of the minimal spike-generating process, which describes the spike train statistically; (2) the randomness (internal entropy rate) of the minimal spike-generating process; and (3) a residual pure noise term not described by the minimal spike-generating process. We use CSMs to approximate each of these quantities. The CSMs are inferred nonparametrically from the data, making only mild regularity assumptions, via the causal state splitting reconstruction algorithm. The methods presented here complement more traditional spike train analyses by describing not only spiking probability and spike train entropy, but also the complexity of a spike train's structure. We demonstrate our approach using both simulated spike trains and experimental data recorded in rat barrel cortex during vibrissa stimulation.