Paramedian Lobule Research Articles

Stereo electroencephalography-guided radiofrequency ablation in focal epilepsia partialis continua: illustrative case.

Epilepsia partialis continua (EPC) is a variant of focal motor status epilepticus that can occur as a single or repetitive episode with progressive or nonprogressive characteristics. The authors describe the feasibility of identifying focal EPC in a 33-year-old woman using video electroencephalography (VEEG), electroencephalography source localization, [18F]fluorodeoxyglucose positron emission tomography, magnetic resonance imaging, and psychiatric and neuropsychological assessments and of treating it with stereo electroencephalography-guided radiofrequency (SEEG-RF) ablation. EPC comprised recurrent myoclonus of the right thigh and iliopsoas with a progressive pain syndrome after left anterior-temporo-mesial resection. Switching between VEEG under regular and epidural block helped to define myoclonus as the presenting ictal symptom with a suspected seizure onset zone in the left parietal paramedian lobule. After the epileptic network was identified, SEEG-RF ablation abolished all seizures. No correlation was found between pain and VEEG/SEEG abnormalities. Rehabilitation began 3 days after the SEEG-RF ablation. By 1 year of follow-up, the patient had no EPC and could walk with assistance in rehabilitation; however, due to the abrupt abolishment of EPC and underlying psychological factors, the patient perceived her pain as overriding, which prevented her from walking. The application of SEEG-RF ablation is an efficient therapeutic option for focal EPC with special concerns regarding concurrent nonepileptic pain. https://thejns.org/doi/10.3171/CASE23611.

Sensorimotor content of multi-unit activity recorded in the paramedian lobule of the cerebellum using carbon fiber microelectrode arrays.

The cerebellum takes in a great deal of sensory information from the periphery and descending signals from the cerebral cortices. It has been debated whether the paramedian lobule (PML) in the rat and its paravermal regions that project to the interpositus nucleus (IPN) are primarily involved in motor execution or motor planning. Studies that have relied on single spike recordings in behaving animals have led to conflicting conclusions regarding this issue. In this study, we tried a different approach and investigated the correlation of field potentials and multi-unit signals recorded with multi-electrode arrays from the PML cortex along with the forelimb electromyography (EMG) signals in rats during behavior. Linear regression was performed to predict the EMG signal envelopes using the PML activity for various time shifts (±25, ±50, ±100, and ± 400 ms) between the two signals to determine a causal relation. The highest correlations (~0.5 on average) between the neural and EMG envelopes were observed for zero and small (±25 ms) time shifts and decreased with larger time shifts in both directions, suggesting that paravermal PML is involved both in processing of sensory signals and motor execution in the context of forelimb reaching behavior. EMG envelopes were predicted with higher success rates when neural signals from multiple phases of the behavior were utilized for regression. The forelimb extension phase was the most difficult to predict while the releasing of the bar phase prediction was the most successful. The high frequency (>300 Hz) components of the neural signal, reflecting multi-unit activity, had a higher contribution to the EMG prediction than did the lower frequency components, corresponding to local field potentials. The results of this study suggest that the paravermal PML in the rat cerebellum is primarily involved in the execution of forelimb movements rather than the planning aspect and that the PML is more active at the initiation and termination of the behavior, rather than the progression.

Single axonal characterization of trigeminocerebellar projection patterns in the mouse.

The cerebellar projection from the trigeminal nuclear complex is one of the major populations of the cerebellar inputs. Although this projection is essential in cerebellar functional processing and organization, its morphological organization has not been systematically clarified. The present study addressed this issue by lobule-specific retrograde neuronal labeling and single axonal reconstruction with anterograde labeling. The cerebellar projection arose mainly from the interpolaris subdivision of the spinal trigeminal nucleus (Sp5I) and the principal trigeminal sensory nucleus (Pr5). Although crus II, paramedian lobule, lobule IX, and simple lobule were the major targets, paraflocculus, and other lobules received some projections. Reconstructed single trigeminocerebellar axons showed 77.8 mossy fiber terminals on average often in multiple lobules but no nuclear collaterals. More terminals were located in zebrin-negative or lightly-positive compartments than in zebrin-positive compartments. While Pr5 axons predominantly projected to ipsilateral crus II, Sp5I axons projected either predominantly to crus II and paramedian lobule often bilaterally, or predominantly to lobule IX always ipsilaterally. Lobule IX-predominant-type Sp5I neurons specifically expressed Gpr26. Gpr26-tagged neuronal labeling produced a peculiar mossy fiber distribution, which was dense in the dorsolateral lobule IX and extending transversely to the dorsal median apex in lobule IX. The projection to the cerebellar nuclei was observed in collaterals of ascending Sp5I axons that project to the diencephalon. In sum, multiple populations of trigeminocerebellar projections showed divergent projections to cerebellar lobules. The projection was generally complementary with the pontine projection and partly matched with the reported orofacial receptive field arrangement.

Whisker kinematics in the cerebellum.

The whisker system is widely used as a model system for understanding sensorimotor integration. Purkinje cells in the crus regions of the cerebellum have been reported to linearly encode whisker midpoint, but it is unknown whether the paramedian and simplex lobules as well as their target neurons in the cerebellar nuclei also encode whisker kinematics and if so which ones. Elucidating how these kinematics are represented throughout the cerebellar hemisphere is essential for understanding how the cerebellum coordinates multiple sensorimotor modalities. Exploring the cerebellar hemisphere of mice using optogenetic stimulation, we found that whisker movements can be elicited by stimulation of Purkinje cells in not only crus1 and crus2, but also in the paramedian lobule and lobule simplex; activation of cells in the medial paramedian lobule had on average the shortest latency, whereas that of cells in lobule simplex elicited similar kinematics as those in crus1 and crus2. During spontaneous whisking behaviour, simple spike activity correlated in general better with velocity than position of the whiskers, but it varied between protraction and retraction as well as per lobule. The cerebellar nuclei neurons targeted by the Purkinje cells showed similar activity patterns characterized by a wide variety of kinematic signals, yet with a dominance for velocity. Taken together, our data indicate that whisker movements are much more prominently and diversely represented in the cerebellar cortex and nuclei than assumed, highlighting the rich repertoire of cerebellar control in the kinematics of movements that can be engaged during coordination. KEY POINTS: Excitation of Purkinje cells throughout the cerebellar hemispheres induces whisker movement, with the shortest latency and longest duration within the paramedian lobe. Purkinje cells have differential encoding for the fast and slow components of whisking. Purkinje cells encode not only the position but also the velocity of whiskers. Purkinje cells with high sensitivity for whisker velocity are preferentially located in the medial part of lobule simplex, crus1 and lateral paramedian. In the downstream cerebellar nuclei, neurons with high sensitivity for whisker velocity are located at the intersection between the medial and interposed nucleus.

Corticosterone effects on postnatal cerebellar development in mice

Glucocorticoids administered early in infancy can affect the architectonic organization of brain structures, particularly those with a postnatal development and resulting in long-term deficits of neuromotor function and cognition. The present study was undertaken to study the effects of daily corticosterone (CORT) injections at a pharmacological dose from postnatal days 8–15 on cerebellar and hippocampal development in mouse pups. Gene expression status for trophic factors involved in synaptic development and function as well as measures of layer thickness associated with cytochrome oxidase labelling were analyzed in the hippocampus, hypothalamus, and specific cerebellar lobules involved in motor control. Repeated CORT injections dysregulated the HPA axis with increased Crh and Nr3c1 mRNA levels in the hypothalamus and a resulting higher serum corticosterone level. The CORT treatment altered the morphology of the hippocampus and down-regulated gene transcription for corticotropin-releasing hormone (Crh) and its type-1 receptor (Crhr1), glucocorticoid receptor (Nr3c1), and brain-derived neurotrophic factor Bdnf and its receptor Ntrk2 (neurotrophic receptor tyrosine kinase 2). Similar mRNA expression decreases were found in the cerebellum for Crhr1, Crhr2, Nr3c1, and Grid2 (glutamatergic δ2 receptor). Morphological alterations and metabolic activity variations were observed in specific cerebellar lobules involved in motor control. The paramedian lobule, normally characterized by mitotic activity in the external germinative layer during the second postnatal week, was atrophic but metabolically hyperactive in its granule cell and molecular layers. On the contrary, lobules with an earlier cell proliferation displayed neurogenesis but a hypoactivated granule cell layer, suggesting a developmental delay in synaptogenesis. The results indicate that glucocorticoid, administered daily during the second postnatal week modulated the developmental programming of the hippocampus and cerebellum. These growth and metabolic alterations may lead possibly to morphological and functional changes later in life.

Developmental Changes in the Thickness of the Cortex and Its Layers in the Paramedian Lobule of the Cerebellum in Children

Developmental Changes in the Thickness of the Cortex and Its Layers in the Paramedian Lobule of the Cerebellum in Children

Distinct proportions of cholinergic neurons in the rat prepositus hypoglossi nucleus according to their cerebellar projection targets.

Cerebellar functions are modulated by cholinergic inputs, the density of which varies among cerebellar regions. Although the prepositus hypoglossi nucleus (PHN), a brainstem structure involved in controlling gaze holding, is known as one of the major sources of these cholinergic inputs, the proportions of cholinergic neurons in PHN projections to distinct cerebellar regions have not been quantitatively analyzed. In this study, we identified PHN neurons projecting to the cerebellum by applying retrograde labeling with dextran-conjugated Alexa 488 in choline acetyltransferase (ChAT)-tdTomato transgenic rats and compared the proportion of cholinergic PHN neurons in the PHN projections to four different regions of the cerebellum, namely the flocculus (FL), the uvula and nodulus (UN), lobules III-V in the vermis (VM), and the hemispheric paramedian lobule and crus 2 (PC). In the PHN, the percentage of cholinergic PHN neurons was lower in the projection to the FL than in the projection to the UN, VM or PC. Preposito-cerebellar neurons, except for preposito-FL neurons, included different proportions of cholinergic neurons at different rostrocaudal positions in the PHN. These results suggest that cholinergic PHN neurons project to not only the vestibulocerebellum but also the anterior vermis and posterior hemisphere and that the proportion of cholinergic neurons among projection neurons from the PHN differs depending on cerebellar target areas and the rostro-caudal regions of the PHN. This study provides insights regarding the involvement of cerebellar cholinergic networks in gaze holding.

Asymmetry of Cerebellar Lobular Development in Ferrets

The ferret cerebellum is anteriorly right-lateralized and posteriorly left-lateralized. This study characterized the left/right difference in ferret cerebellar lobular morphology using 3D-rendered magnetic resonance images of fixed brains from seven male and seven female ferrets on postnatal day 90. Asymmetrical lobular morphology showed asymmetrical sublobular development in the anterior vermis, lobulus simplex, and ansiform lobules and additional grooves asymmetrically appearing in the paramedian lobule, lobule VI, and ansiform lobules. Although we observed these asymmetric hallmarks in four cerebellar transverse domains in both sexes, there was no left/right difference in their incidence in each domain. Males showed a significantly higher incidence of the additional grooves in the left side of the ansiform lobules than in females. Data were combined and classified as per the asymmetry quotient (AQ) into left- (AQ < 0) and right-dominant (AQ > 0) groups. There were significantly higher incidences of poor sublobular development of ansiform lobules and additional groove appearing in lobule VI on the right than on the left in the left-dominant group. Asymmetric hallmarks visible on the cerebellar surface of ferrets are relevant to the left-biased volume asymmetry of the central zone of cerebellar transversus domains containing lobule VI and ansiform lobules.

Structural Transformations in Neural Clusters of the Cerebral and Cerebellar Cortex in Children

Objective – the study of age-related changes in neural groups of the cerebral cortex and cerebellar cortex in the process of upward ontogenesis. Material and methods . The work was done on post-mortal material (75 left cerebral hemispheres, 62 cerebellum) obtained from children from birth to 12 years old who died as a result of injuries without damage to the brain. Using computer morphometry on the Nissl stained frontal histological sections of the cerebral cortex taken in layer III of fields 8, 6o р and 37ac, as well as in the granular layer of the paramedian lobule of the cerebellar cortex (H VII B), the area of the neural group on the section and the total area of neurons were measured as part of a grouping. Quantitative data analysis was carried out using variation statistics in annual intervals. Results . In children from birth to 12 years, in the dynamics of developmental changes in the microstructure of the cerebral and cerebellar cortical zones associated with visual-spatial perception, 4 stages of quantitative changes in the cluster (ensemble) organization of the cortex are distinguished: I - from birth to the end of 1 year of life, II – from 1 to the end of 2 years, III – from 3 to 5–6 years, IV – from 5–6 to 8–9 years. In the cerebellum cortex, significant changes in the structure of neural clusters are observed by the end of 1 year of life, by 3 and by 5–6 years. Structural changes in neural groups differ in terms and intensity in each of the studied fields. Conclusion . The sizes of neural clusters in the microstructure of the cerebral and cerebellar cortex are informative indicators for identifying the stages of significant age-related transformations in different zones of the human cortical formations in postnatal ontogenesis, and can be recommended for use in comparative anatomical and clinical studies.

Modulation of Multiunit Spike Activity by Transcranial AC Stimulation (tACS) in the Rat Cerebellar Cortex.

Transcranial electrical stimulation (tES) techniques have garnered significant interest due to their non-invasiveness and potential to offer a treatment option in a wide variety of brain disorders. Among several modulation techniques, transcranial alternating current stimulation (tACS) is favored for its ability to entrain the neural oscillations. The cerebellum is one of the targeted sites because of its involvement in motor and cognitive functions. However, animal studies are lacking in the literature looking into the mechanism of action in cerebellar tACS. In this study, we used a rat model and monitored the activity of the cerebellar cortex, which sculpts the cerebellar output by adjusting the firing rate and timing of the neurons in the deep cerebellar nuclei (DCN). For neural recording, a tungsten electrode was inserted into the cerebellar cortex through a craniotomy hole located over the right paramedian lobule (PML). A helical Ag/AgCl wire electrode was placed atop the skull near the caudal edge to inject a 1 Hz biphasic sinusoidal current. Our results showed that the multiunit activity (MUA) of the cerebellar cortex was strongly modulated by tACS. The negative phase of the electric current enhanced the neural firing rate while the positive phase suppressed the activity. Furthermore, the spike rate showed modulation by the instantaneous strength of the injected current within the sinusoidal cycle. This warrants research to further look into the mechanism of tACS acting on the cerebellar cortex at the cellular level.

Motor learning induces plastic changes in Purkinje cell dendritic spines in the rat cerebellum

IntroductionThe paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. MethodsAdult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. ResultsThe learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. ConclusionThe initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent “silencing” of memory consolidation processes, based on the regulation of the neuronal excitability.

The entire trajectories of single pontocerebellar axons and their lobular and longitudinal terminal distribution patterns in multiple aldolase C-positive compartments of the rat cerebellar cortex.

The mammalian cerebellar cortex is compartmentalized, both anatomically and histochemically, into multiple parasagittal bands. To characterize the multiple zonal patterns of pontocerebellar mossy fiber projection, single neurons in the basilar pontine nucleus (BPN) were labeled by injecting biotinylated dextran amine into the BPN, and the entire axonal trajectory of single labeled neurons (n = 25) was reconstructed in relation to aldolase C compartments of Purkinje cells in rats. Single pontocerebellar axons, after passing through the contralateral middle cerebellar peduncle, ran transversely in the deep cerebellar white matter toward and often across the midline, and on their ways, gave rise to 2-10 primary collaterals at almost right angles in specific lobules only contralaterally or bilaterally with contralateral predominance. Each primary collateral further branched in a parasagittal plane to form a strip-shaped longitudinal termination zone with rosette-type swellings clustered in aldolase C-positive compartments in a single or multiple lobules, mainly in compartment 4+//5+, 5+//6+, and 6+//7+. Axons arising from the central, rostral, and lateral part of the BPN projected with multiple branches, mainly to simple lobule, crus II and paramedian lobule, to crus I and dorsal paraflocculus, and to ventral paraflocculus and lobule IXc, respectively. The results showed the pontocerebellar projection is closely related to lobular and compartmental organization of the cerebellum. A comparison of single axon morphologies of different mossy fiber systems indicates that the projection pattern of single pontocerebellar neurons with multiple collaterals innervating different longitudinal compartments arranged in a mediolateral direction represents a general feature of mossy fiber projection.

Divergent projections of single pontocerebellar axons to multiple cerebellar lobules in the mouse

The basilar pontine nucleus (PN) is the key relay point for the cerebrocerebellar link. However, the projection pattern of pontocerebellar mossy fiber axons, which is essential in determining the functional organization of the cerebellar cortex, has not been fully clarified. We reconstructed the entire trajectory of 25 single pontocerebellar mossy fiber axons labeled by localized injection of biotinylated dextran amine into various locations in the PN and mapped all their terminals in an unfolded scheme of the cerebellum in 10 mice. The majority of axons (20/25 axons) entered the cerebellum through the middle cerebellar peduncle contralateral to the origin, while others entered through the ipsilateral pathway. A small number of axons (1/25 axons) had collaterals terminating in the cerebellar nuclei. Axons projected mostly to a combination of lobules, often bilaterally, and terminated in multiple zebrin (aldolase C) stripes, more frequently in zebrin-positive stripes (83.9%) than in zebrin-negative stripes, with 66.5 mossy fiber terminals on the average. Axons originating from the rostral (plus medial and lateral), central and caudal PN mainly terminated in the paraflocculus, crus I and lobule VIb-c, in the simplex lobule, crus II and paramedian lobule, and in lobules II-VIa, VIII and copula pyramidis, respectively. The results suggest that the interlobular branching pattern of pontocerebellar axons determines the group of cerebellar lobules that are involved in a related functional localization of the cerebellum. In the hemisphere, crus I may be functionally distinct from neighboring lobules (simple lobule and crus II) in the mouse cerebellum based on the pontocerebellar axonal projection pattern.

Regional and sex-dependent alterations in Purkinje cell density in the valproate mouse model of autism.

Neuropathological and neuroimaging studies indicate a decrease in Purkinje cell (PC) density in the cerebellum of autistic patients and rodent models of autism. Autism is far more prevalent in males than females, and sex-specific properties of PCs have been reported recently. We investigated the differential sensitivity of PCs in the valproate acid (VPA) mouse model of autism by estimating the linear density of PCs immununolabelled with calbindin in the cerebellum of males and females. Whereas prenatal VPA treatment surprisingly increased PC linear density in both sexes 13 days after birth (P13), it significantly reduced the linear density of PCs in the cerebellum of 40-day-old (P40) males, but not females. In males, PC loss was more pronounced in the posterior part of the cerebellum and was significant in the VIth, VIIth, IXth and paramedian lobules. In females, PC loss was restricted to the paramedian lobule. These results suggest that this sex-specific sensitivity of PCs to VPA may contribute towards the motor disturbances and behavioural abnormalities observed in autism.

The tree shrew cerebellum atlas: Systematic nomenclature, neurochemical characterization, and afferent projections.

The cerebellum is involved in the control of movement, emotional responses, and reward processing. The tree shrew is the closest living relative of primates. However, little is known not only about the systematic nomenclature for the tree shrew cerebellum but also about the detailed neurochemical characterization and afferent projections. In this study, Nissl staining and acetylcholinesterase histochemistry were used to reveal anatomical features of the cerebellum of tree shrews (Tupaia belangeri chinensis). The cerebellar cortex presented a laminar structure. The morphological characteristics of the cerebellum were comprehensively described in the coronal, sagittal, and horizontal sections. Moreover, distributive maps of calbindin-immunoreactive (-ir) cells in the Purkinje cell layer of the cerebellum of tree shrews were depicted using coronal, sagittal, and horizontal schematics. In addition, 5th cerebellar lobule (5Cb)-projecting neurons were present in the pontine nuclei, reticular nucleus, spinal vestibular nucleus, ventral spinocerebellar tract, and inferior olive of the tree shrew brain. The anterior part of the paramedian lobule of the cerebellum (PMa) received mainly strong innervation from the lateral reticular nucleus, inferior olive, pontine reticular nucleus, spinal trigeminal nucleus, pontine nuclei, and reticulotegmental nucleus of the pons. The present results provide the first systematic nomenclature, detailed atlas of the whole cerebellum, and whole-brain mapping of afferent projections to the 5Cb and PMa in tree shrews. Our findings provide morphological support for tree shrews as an alternative model for studies of human cerebellar pathologies.

El aprendizaje motor induce cambios plásticos en las espinas dendríticas de las células de Purkinje del cerebelo de ratas

IntroductionThe paramedian lobule of the cerebellum is involved in learning to correctly perform motor skills through practice. Dendritic spines are dynamic structures that regulate excitatory synaptic stimulation. We studied plastic changes occurring in the dendritic spines of Purkinje cells from the paramedian lobule of rats during motor learning. MethodsAdult male rats were trained over a 6-day period using an acrobatic motor learning paradigm; the density and type of dendritic spines were determined every day during the study period using a modified version of the Golgi method. ResultsThe learning curve reflected a considerable decrease in the number of errors made by rats as the training period progressed. We observed more dendritic spines on days 2 and 6, particularly more thin spines on days 1, 3, and 6, fewer mushroom spines on day 3, fewer stubby spines on day 1, and more thick spines on days 4 and 6. ConclusionThe initial stage of motor learning may be associated with fast processing of the underlying synaptic information combined with an apparent “silencing” of memory consolidation processes, based on the regulation of the neuronal excitability.

Disynaptic Subthalamic Input to the Posterior Cerebellum in Rat.

In the last decade, the interplay between basal ganglia and cerebellar functions has been increasingly advocated to explain their joint operation in both normal and pathological conditions. Yet, insight into the neuroanatomical basis of this interplay between both subcortical structures remains sparse and is mainly derived from work in primates. Here, in rodents, we have studied the existence of a potential disynaptic connection between the subthalamic nucleus (STN) and the cerebellar cortex as has been demonstrated earlier for the primate. A mixture of unmodified rabies virus (RABV: CVS 11) and cholera toxin B-subunit (CTb) was injected at places in the posterior cerebellar cortex of nine rats. The survival time was chosen to allow for disynaptic retrograde transneuronal infection of RABV. We examined the STN for neurons infected with RABV in all nine cases and related the results with the location of the RABV/CTb injection site, which ranged from the vermis of lobule VII, to the paravermis and hemispheres of the paramedian lobule and crus 2a. We found that cases with injection sites in the vermis of lobule VII showed prominent RABV labeling in the STN. In contrast, almost no subthalamic labeling was noted in cases with paravermal or hemispheral injection sites. We show circumstantial evidence that not only the pontine nuclei but also the pedunculotegmental nucleus may act as the intermediary in the connection from STN to cerebellar cortex. This finding implies that in the rat the STN links disynaptically to the vermal part of lobule VII of the cerebellar cortex, without any major involvement of the cerebellar areas that are linked to sensorimotor functions. As vermal lobule VII recently has been shown to process disynaptic input from the retrosplenial and orbitofrontal cortices, we hypothesize that in the rat the subthalamic input to cerebellar function might be used to influence more prominently non-motor functions of the cerebellum than motor functions. This latter aspect seems to contradict the primate results and could point to a more elaborate interaction between basal ganglia and cerebellum in more demanding motor tasks.

High frequency synchrony in the cerebellar cortex during goal directed movements.

The cerebellum is involved in sensory-motor integration and cognitive functions. The origin and function of the field potential oscillations in the cerebellum, especially in the high frequencies, have not been explored sufficiently. The primary objective of this study was to investigate the spatio-temporal characteristics of high frequency field potentials (150–350 Hz) in the cerebellar cortex in a behavioral context. To this end, we recorded from the paramedian lobule in rats using micro electro-corticogram (μ-ECoG) electrode arrays while the animal performed a lever press task using the forelimb. The phase synchrony analysis shows that the high frequency oscillations recorded at multiple points across the paramedian cortex episodically synchronize immediately before and desynchronize during the lever press. The electrode contacts were grouped according to their temporal course of phase synchrony around the time of lever press. Contact groups presented patches with slightly stronger synchrony values in the medio-lateral direction, and did not appear to form parasagittal zones. The size and location of these patches on the cortical surface are in agreement with the sensory evoked granular layer patches originally reported by Welker's lab (Shambes et al., 1978). Spatiotemporal synchrony of high frequency field potentials has not been reported at such large-scales previously in the cerebellar cortex.

Electrophysiological monitoring of injury progression in the rat cerebellar cortex.

The changes of excitability in affected neural networks can be used as a marker to study the temporal course of traumatic brain injury (TBI). The cerebellum is an ideal platform to study brain injury mechanisms at the network level using the electrophysiological methods. Within its crystalline morphology, the cerebellar cortex contains highly organized topographical subunits that are defined by two main inputs, the climbing (CFs) and mossy fibers (MFs). Here we demonstrate the use of cerebellar evoked potentials (EPs) mediated through these afferent systems for monitoring the injury progression in a rat model of fluid percussion injury (FPI). A mechanical tap on the dorsal hand was used as a stimulus, and EPs were recorded from the paramedian lobule (PML) of the posterior cerebellum via multi-electrode arrays (MEAs). Post-injury evoked response amplitudes (EPAs) were analyzed on a daily basis for 1 week and compared with pre-injury values. We found a trend of consistently decreasing EPAs in all nine animals, losing as much as 72 ± 4% of baseline amplitudes measured before the injury. Notably, our results highlighted two particular time windows; the first 24 h of injury in the acute period and day-3 to day-7 in the delayed period where the largest drops (~50% and 24%) were observed in the EPAs. In addition, cross-correlations of spontaneous signals between electrode pairs declined (from 0.47 ± 0.1 to 0.35 ± 0.04, p < 0.001) along with the EPAs throughout the week of injury. In support of the electrophysiological findings, immunohistochemical analysis at day-7 post-injury showed detectable Purkinje cell loss at low FPI pressures and more with the largest pressures used. Our results suggest that sensory evoked potentials (SEPs) recorded from the cerebellar surface can be a useful technique to monitor the course of cerebellar injury and identify the phases of injury progression even at mild levels.

Specific regions display altered grey matter volume in μ-opioid receptor knockout mice: MRI voxel-based morphometry.

μ Opioid receptor knockout (MOP-KO) mice display several behavioural differences from wild-type (WT) littermates including differential responses to nociceptive stimuli. Brain structural changes have been tied to behavioural alterations noted in transgenic mice with targeting of different genes. Hence, we assess the brain structure of MOP-KO mice. Magnetic resonance imaging (MRI) voxel-based morphometry (VBM) and histological methods were used to identify structural differences between extensively backcrossed MOP-KO mice and WT mice. MOP-KO mice displayed robust increases in regional grey matter volume in olfactory bulb, several hypothalamic nuclei, periaqueductal grey (PAG) and several cerebellar areas, most confirmed by VBM analysis. The largest increases in grey matter volume were detected in the glomerular layer of the olfactory bulb, arcuate nucleus of hypothalamus, ventrolateral PAG (VLPAG) and cerebellar regions including paramedian and cerebellar lobules. Histological analyses confirm several of these results, with increased VLPAG cell numbers and increased thickness of the olfactory bulb granule cell layer and cerebellar molecular and granular cell layers. MOP deletion causes previously undescribed structural changes in specific brain regions, but not in all regions with high MOP receptor densities (e.g. thalamus, nucleus accumbens) or that exhibit adult neurogenesis (e.g. hippocampus). Volume differences in hypothalamus and PAG may reflect behavioural changes including hyperalgesia. Although the precise relationship between volume change and MOP receptor deletion was not determined from this study alone, these findings suggest that levels of MOP receptor expression may influence a broader range of neural structure and function in humans than previously supposed. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.