Cortico-cortical Pathways Research Articles

Clustering of tau-immunoreactive pathology in chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disorder which may result from repetitive brain injury. A variety of tau-immunoreactive pathologies are present, including neurofibrillary tangles (NFT), neuropil threads (NT), dot-like grains (DLG), astrocytic tangles (AT), and occasional neuritic plaques (NP). In tauopathies, cellular inclusions in the cortex are clustered within specific laminae, the clusters being regularly distributed parallel to the pia mater. To determine whether a similar spatial pattern is present in CTE, clustering of the tau-immunoreactive pathology was studied in the cortex, hippocampus, and dentate gyrus in 11 cases of CTE and 7 cases of Alzheimer's disease neuropathologic change (ADNC) without CTE. In CTE: (1) all aspects of tau-immunoreactive pathology were clustered and the clusters were frequently regularly distributed parallel to the tissue boundary, (2) clustering was similar in two CTE cases with minimal co-pathology compared with cases with associated ADNC or TDP-43 proteinopathy, (3) in a proportion of cortical gyri, estimated cluster size was similar to that of cell columns of the cortico-cortical pathways, and (4) clusters of the tau-immunoreactive pathology were infrequently spatially correlated with blood vessels. The NFT and NP in ADNC without CTE were less frequently randomly or uniformly distributed and more frequently in defined clusters than in CTE. Hence, the spatial pattern of the tau-immunoreactive pathology observed in CTE is typical of the tauopathies but with some distinct differences compared to ADNC alone. The spread of pathogenic tau along anatomical pathways could be a factor in the pathogenesis of the disease.

High-order motor cortex in rats receives somatosensory inputs from the primary motor cortex via cortico-cortical pathways.

The motor cortex of rats contains two forelimb motor areas; the caudal forelimb area (CFA) and the rostral forelimb area (RFA). Although the RFA is thought to correspond to the premotor and/or supplementary motor cortices of primates, which are higher-order motor areas that receive somatosensory inputs, it is unknown whether the RFA of rats receives somatosensory inputs in the same manner. To investigate this issue, voltage-sensitive dye (VSD) imaging was used to assess the motor cortex in rats following a brief electrical stimulation of the forelimb. This procedure was followed by intracortical microstimulation (ICMS) mapping to identify the motor representations in the imaged cortex. The combined use of VSD imaging and ICMS revealed that both the CFA and RFA received excitatory synaptic inputs after forelimb stimulation. Further evaluation of the sensory input pathway to the RFA revealed that the forelimb-evoked RFA response was abolished either by the pharmacological inactivation of the CFA or a cortical transection between the CFA and RFA. These results suggest that forelimb-related sensory inputs would be transmitted to the RFA from the CFA via the cortico-cortical pathway. Thus, the present findings imply that sensory information processed in the RFA may be used for the generation of coordinated forelimb movements, which would be similar to the function of the higher-order motor cortex in primates.

Regional variation of white matter development in the cat brain revealed by ex vivo diffusion MR tractography

Three-dimensional reconstruction of developing fiber pathways is essential to assessing the developmental course of fiber pathways in the whole brain. We applied diffusion spectrum imaging (DSI) tractography to five juvenile ex vivo cat brains at postnatal day (P) 35, when the degree of myelination varies across brain regions. We quantified diffusion properties (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]) and other measurements (number, volume, and voxel count) on reconstructed pathways for projection (cortico-spinal and thalamo-cortical), corpus callosal, limbic (cingulum and fornix), and association (cortico-cortical) pathways, and characterized regional differences in maturation patterns by assessing diffusion properties. FA values were significantly higher in cortico-cortical pathways within the right hemisphere compared to those within the left hemisphere, while the other measurements for the cortico-cortical pathways within the hemisphere did not show asymmetry. ADC values were not asymmetric in both types of pathways. Interestingly, tract count and volume were significantly larger in the left thalamo-cortical pathways compared to the right thalamo-cortical pathways. The bilateral thalamo-cortical pathways showed high FA values compared to the other fiber pathways. On the other hand, ADC values did not show any differences across pathways studied. These results demonstrate that DSI tractography successfully depicted regional variations of white matter tracts during development when myelination is incomplete. Low FA and high ADC values in the cingulum bundle suggest that the cingulum bundle is less mature than the others at this developmental stage.

Organization of cortico-cortical pathways supporting memory retrieval across subregions of the left ventrolateral prefrontal cortex.

Functional magnetic resonance imaging (fMRI) evidence indicates that different subregions of ventrolateral prefrontal cortex (VLPFC) participate in distinct cortical networks. These networks have been shown to support separable cognitive functions: anterior VLPFC [inferior frontal gyrus (IFG) pars orbitalis] functionally correlates with a ventral fronto-temporal network associated with top-down influences on memory retrieval, while mid-VLPFC (IFG pars triangularis) functionally correlates with a dorsal fronto-parietal network associated with postretrieval control processes. However, it is not known to what extent subregional differences in network affiliation and function are driven by differences in the organization of underlying white matter pathways. We used high-angular-resolution diffusion spectrum imaging and functional connectivity analysis in unanesthetized humans to address whether the organization of white matter connectivity differs between subregions of VLPFC. Our results demonstrate a ventral-dorsal division within IFG. Ventral IFG as a whole connects broadly to lateral temporal cortex. Although several different individual white matter tracts form connections between ventral IFG and lateral temporal cortex, functional connectivity analysis of fMRI data indicates that these are part of the same ventral functional network. By contrast, across subdivisions, dorsal IFG was connected with the midfrontal gyrus and correlated as a separate dorsal functional network. These qualitative differences in white matter organization within larger macroanatomical subregions of VLPFC support prior functional distinctions among these regions observed in task-based and functional connectivity fMRI studies. These results are consistent with the proposal that anatomical connectivity is a crucial determinant of systems-level functional organization of frontal cortex and the brain in general.

Reduced afferent-induced facilitation of primary motor cortex excitability in restless legs syndrome

Restless legs syndrome (RLS) is characterized by the association of an urge to move, and vesperal or nocturnal sensory symptoms; it is frequently associated with periodic limb movements. Evidence from imaging and electrophysiological studies suggests that RLS is linked to changes in sensorimotor integration. Nevertheless, the underlying mechanisms have not been characterized, and the cortical origin has yet to be confirmed.The objective of the present study was to establish whether or not sensorimotor integration in RLS patients is impaired in the evening. The time-dependent modulation of motor cortex excitability following peripheral electric nerve stimulation was studied in 14 idiopathic RLS patients, and 14 paired healthy controls. Different inter-stimulus intervals were used to measure short-latency and long-latency afferent inhibition (SAI and LAI) and afferent-induced facilitation (AIF). Motor evoked potentials were recorded from the first dorsal interosseous muscle in two experimental sessions (one in the morning and one in the evening).With the exception of LAI (which was present in the morning but absent in the evening in both healthy controls and RLS patients), no circadian variations were observed in sensorimotor integration. Although SAI was present in patients with RLS, AIF was disrupted (relative to controls) – suggesting the presence of an indirect sensorimotor integration disorder affecting the long corticocortical pathways in patients with RLS. The lack of circadian modulation in sensorimotor integration suggests that clinical circadian variations have other causes.

Different Roles of Direct and Indirect Frontoparietal Pathways for Individual Working Memory Capacity.

The ability to temporarily store and manipulate information in working memory is a hallmark of human intelligence and differs considerably across individuals, but the structural brain correlates underlying these differences in working memory capacity (WMC) are only poorly understood. In two separate studies, diffusion MRI data and WMC scores were collected for 70 and 109 healthy individuals. Using a combination of probabilistic tractography and network analysis of the white matter tracts, we examined whether structural brain network properties were predictive of individual WMC. Converging evidence from both studies showed that lateral prefrontal cortex and posterior parietal cortex of high-capacity individuals are more densely connected compared with low-capacity individuals. Importantly, our network approach was further able to dissociate putative functional roles associated with two different pathways connecting frontal and parietal regions: a corticocortical pathway and a subcortical pathway. In Study 1, where participants were required to maintain and update working memory items, the connectivity of the direct and indirect pathway was predictive of WMC. In contrast, in Study 2, where participants were required to maintain working memory items without updating, only the connectivity of the direct pathway was predictive of individual WMC. Our results suggest an important dissociation in the circuitry connecting frontal and parietal regions, where direct frontoparietal connections might support storage and maintenance, whereas subcortically mediated connections support the flexible updating of working memory content.

Familiarity modulates motor activation while other species' actions are observed: a magnetic stimulation study.

Observing other people's actions facilitates the observer's motor system as compared with observing the same individuals at rest. This motor activation is thought to result from mirror-like activity in fronto-parietal areas, which enhances the excitability of the primary motor cortex via cortico-cortical pathways. Although covert motor activation in response to observed actions has been widely investigated between conspecifics, how humans cope with other species' actions has received less attention. For example, it remains unclear whether the human motor system is activated by observing other species' actions, and whether prior familiarity with the non-conspecific agent modulates this activation. Here, we combined single-pulse transcranial magnetic stimulation and motor-evoked potential recording to explore the impact of familiarity on motor activation during the observation of non-conspecific actions. Videos displaying actions performed either by a conspecific (human) or by a non-conspecific (dog) were shown to individuals who had prior familiarity or no familiarity at all with the non-conspecific agent. We found that, whereas individuals with long-lasting familiarity showed similar levels of motor activation for human and canine actions, individuals who had no familiarity showed higher motor activation for human than for canine actions. These findings suggest that the human motor system is flexible enough to resonate with other species, and that familiarity plays a key role in tuning this ability.

Selection of cortical dynamics for motor behaviour by the basal ganglia

The basal ganglia and cortex are strongly implicated in the control of motor preparation and execution. Re-entrant loops between these two brain areas are thought to determine the selection of motor repertoires for instrumental action. The nature of neural encoding and processing in the motor cortex as well as the way in which selection by the basal ganglia acts on them is currently debated. The classic view of the motor cortex implementing a direct mapping of information from perception to muscular responses is challenged by proposals viewing it as a set of dynamical systems controlling muscles. Consequently, the common idea that a competition between relatively segregated cortico-striato-nigro-thalamo-cortical channels selects patterns of activity in the motor cortex is no more sufficient to explain how action selection works. Here, we contribute to develop the dynamical view of the basal ganglia–cortical system by proposing a computational model in which a thalamo-cortical dynamical neural reservoir is modulated by disinhibitory selection of the basal ganglia guided by top-down information, so that it responds with different dynamics to the same bottom-up input. The model shows how different motor trajectories can so be produced by controlling the same set of joint actuators. Furthermore, the model shows how the basal ganglia might modulate cortical dynamics by preserving coarse-grained spatiotemporal information throughout cortico-cortical pathways.Electronic supplementary materialThe online version of this article (doi:10.1007/s00422-015-0662-6) contains supplementary material, which is available to authorized users.

Spatiotemporal Profile of Voltage-Sensitive Dye Responses in the Visual Cortex of Tree Shrews Evoked by Electric Microstimulation of the Dorsal Lateral Geniculate and Pulvinar Nuclei.

The pulvinar nucleus represents the main extrageniculate thalamic visual structure in higher-order mammals, but its exact role remains enigmatic. The pulvinar receive prominent inputs from virtually all visual cortical areas. Cortico-thalamo-cortical pathways through the pulvinar nuclei may then provide a complementary route for corticocortical information flow. One step toward the understanding of the role of transthalamic corticocortical pathways is to determine the nature of the signals transmitted between the cortex and the thalamus. By performing, for the first time, high spatiotemporal mesoscopic imaging on tree shrews (the primate's closest relative) through the combination of voltage-sensitive dye recordings and brain stimulation, we revealed clear evidence of distinct thalamocortical functional connectivity pattern originating from the geniculate nucleus and the pulvinar nuclei.

Altered white matter in early visual pathways of humans with amblyopia

Amblyopia is a visual disorder caused by poorly coordinated binocular input during development. Little is known about the impact of amblyopia on the white matter within the visual system. We studied the properties of six major visual white-matter pathways in a group of adults with amblyopia (n=10) and matched controls (n=10) using diffusion weighted imaging (DWI) and fiber tractography. While we did not find significant differences in diffusion properties in cortico-cortical pathways, patients with amblyopia exhibited increased mean diffusivity in thalamo-cortical visual pathways. These findings suggest that amblyopia may systematically alter the white matter properties of early visual pathways.

Applications of closed-loop approaches to therapeutic brain stimulation

Event Abstract Back to Event Applications of closed-loop approaches to therapeutic brain stimulation Randolph Nudo1* 1 University of Kansas Medical Center, Department of Rehabilitation Medicine, United States Artificial modulation of neural activity following acquired central nervous system injuries has received increasing attention over the past several years as therapeutic interventions. Examples include numerous non-invasive approaches, including transcranial magnetic stimulation or transcranial direct current stimulation to excite or suppress neuronal activity in the damaged or intact cortex after stroke. More invasive technologies, such as epidural stimulation, vagus nerve stimulation and deep brain stimulation, also have demonstrated promising results in neurological populations. Most of these neuromodulation therapies have employed continuous stimulation, and indications in research settings continue to expand for these neuromodulatory therapies. However, recently, various implementations of closed-loop approaches have begun to attract attention for altering neuronal function. These closed-loop modalities are often described as responsive neurostimulation, adaptive brain stimulation or activity-dependent stimulation (ADS), and typically involve invasive technologies. For example, subdural or epidural electrodes have been used to record electroencephalographic activity, triggering brain stimulation when epileptiform discharges are detected to suppress a seizure. In animal models, it has long been known that synaptic facilitation can be induced with particular patterns of open-loop stimulation (e.g., theta burst stimulation), or by spike-timing dependent stimulation. Recent studies using ADS have been used in our laboratory to reinforce synaptic activity in specific cortico-cortical pathways following cortical injury. Such closed-loop stimulation resulted in rapid recovery of sensorimotor skills in rats (Guggenmos et al. 2013, PNAS). We have recently found that cortico-cortical functional connectivity can be reinforced in either intact or injured brains, even under anesthesia, providing a convenient platform for testing hypotheses regarding spike-timing dependent plasticity in neuronal systems. These results suggest that cortico-cortical entrainment immediately after cortical injury can be evoked more readily than in healthy brains. However, cortico-cortical potentiation appears to differ depending upon pre-existing strength of anatomical connectivity between the areas. These results are placed in the context of diaschisis-like phenomena that result from focal injury. Conference: 2015 International Workshop on Clinical Brain-Machine Interfaces (CBMI2015), Tokyo, Japan, 13 Mar - 15 Mar, 2015. Presentation Type: Oral presentation / lecture Topic: Clinical Brain-Machine Interfaces Citation: Nudo R (2015). Applications of closed-loop approaches to therapeutic brain stimulation. Conference Abstract: 2015 International Workshop on Clinical Brain-Machine Interfaces (CBMI2015). doi: 10.3389/conf.fnhum.2015.218.00015 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 23 Apr 2015; Published Online: 29 Apr 2015. * Correspondence: PhD. Randolph Nudo, University of Kansas Medical Center, Department of Rehabilitation Medicine, Kansas City, KS, 66103, United States, randynudo@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Randolph Nudo Google Randolph Nudo Google Scholar Randolph Nudo PubMed Randolph Nudo Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Broca’s area – Thalamic connectivity

Broca’s area is crucially involved in language processing. The sub-regions of Broca’s area (pars triangularis, pars opercularis) presumably are connected via corticocortical pathways. However, growing evidence suggests that the thalamus may also be involved in language and share some of the linguistic functions supported by Broca’s area. Functional connectivity is thought to be achieved via corticothalamic/thalamocortical white matter pathways. Our study investigates structural connectivity between Broca’s area and the thalamus, specifically ventral anterior nucleus and pulvinar. We demonstrate that Broca’s area shares direct connections with these thalamic nuclei and suggest a local Broca’s area—thalamus network potentially involved in linguistic processing. Thalamic connectivity with Broca’s area may serve to selectively recruit cortical regions storing multimodal features of lexical items and to bind them together during lexical–semantic processing. In addition, Broca’s area—thalamic circuitry may enable cortico–thalamo–cortical information transfer and modulation between BA 44 and 45 during language comprehension and production.

Effects of dopaminergic treatment on functional cortico-cortical connectivity in Parkinson's disease.

Interactions between dorsal premotor cortex (PMd) and primary motor cortex (M1) and interhemispheric inhibition (IHI) between M1 are impaired in Parkinson's disease (PD). We used dual-site transcranial magnetic stimulation to compare effects of first-time levodopa application with chronic dopaminergic therapy on these interactions in PD. Twelve untreated PD patients were studied before and after their first-ever intake of levodopa. The effects of chronic dopaminergic medication were evaluated in 11 patients who had received regular dopaminergic medication for approximately 3 years. Nine of these patients were also measured after overnight withdrawal of medication. For IHI, conditioning stimuli (CS) were applied to left M1 followed by test stimuli (TS) over right M1 and vice versa in separate blocks at interstimulus intervals (ISI) of 6-10 ms. Next, CS were applied to left PMd at subthreshold intensity followed by TS over left M1 at ISIs of 4 and 6 ms. Results were compared to 17 age- and gender-matched controls. In de novo PD patients, levodopa reduced left-to-right IHI, but did not alter PMd-M1 connectivity. In contrast, inhibitory PMd-M1 connectivity was present in early disease patients under chronic dopaminergic stimulation, but not in de novo PD patients at low stimulus intensities at an ISI of 4 ms. First-time exposure to levodopa exerts different effects on cortico-cortical pathways than chronic dopaminergic stimulation in PD, suggesting a change in the responsiveness of cortico-cortical circuits during the course of PD.

The Stimulus Selectivity and Connectivity of Layer Six Principal Cells Reveals Cortical Microcircuits Underlying Visual Processing

SummarySensory computations performed in the neocortex involve layer six (L6) cortico-cortical (CC) and cortico-thalamic (CT) signaling pathways. Developing an understanding of the physiological role of these circuits requires dissection of the functional specificity and connectivity of the underlying individual projection neurons. By combining whole-cell recording from identified L6 principal cells in the mouse primary visual cortex (V1) with modified rabies virus-based input mapping, we have determined the sensory response properties and upstream monosynaptic connectivity of cells mediating the CC or CT pathway. We show that CC-projecting cells encompass a broad spectrum of selectivity to stimulus orientation and are predominantly innervated by deep layer V1 neurons. In contrast, CT-projecting cells are ultrasparse firing, exquisitely tuned to orientation and direction information, and receive long-range input from higher cortical areas. This segregation in function and connectivity indicates that L6 microcircuits route specific contextual and stimulus-related information within and outside the cortical network.

The dorsolateral prefrontal network is involved in pain perception in knee osteoarthritis patients

Functional MRI (fMRI) studies have been used to investigate how the brain processes noxious stimuli in osteoarthritis (OA) and to identify the cortical location of pain perception. However, no consensus has been reached regarding brain activity associated with pain-induced conditions in OA patients. We examined cerebral responses using intra-epidermal electrical stimulation of the . knee in knee OA patients. To replicate the pain of knee OA in terms of predictability, acute pain generated by electrical stimulation was provided simultaneously with displayed images in this study. We used fMRI to identify differences in response between healthy subjects and knee OA patients and explored the modulating cortico-subcortical and cortico-cortical pathways using psychophysiological interaction (PPI) analysis. Our results show that chronic pain results in a different brain activation profile in the DLPFC and the pain matrix in knee OA patients. Abnormal brain connectivity between the DLPFC and the pain matrix is induced by chronic pain in knee OA patients.

Multimodal cortical sensory pathways revealed by sequential transcranial electrical stimulation in mice

We investigated polysynaptic cortical pathways linking primary to multimodal sensory association areas in mice using transcranial flavoprotein imaging combined with sequential application of transcranial electrical stimulation (TES). Stimulation of primary visual cortex (V1) elicited activity in lateral and medial areas of secondary visual cortices (V2), which were reciprocally connected. Stimulation of V2 areas elicited activity in area 2. Similarly, corticocortical pathways from primary somatosensory cortex (S1) through the corresponding secondary somatosensory areas (S2) to area 2 were observed. Auditory pathways from primary auditory area (A1) through peripheral region (area 22) to area 2 and from anterior auditory field to area 2 were also found. Stimulation in area 2 elicited activity in part of parietal association cortex (PtA), which was reciprocally connected with area 2, and in some areas near the midline including retrosplenial cortex (RSA). A cortical pathway from RSA through anterior cingulate cortex (aCC) to frontal areas was also visualized. These results indicate that area 2, surrounded by visual, somatosensory and auditory cortices, may receive inputs from all three primary sensory areas, and may send outputs through the parietal association cortex to frontal areas, suggesting that area 2 may have an important role in multimodal sensory integration in mice.

Compensatory plasticity: time matters.

Plasticity in the human and animal brain is the rule, the base for development, and the way to deal effectively with the environment for making the most efficient use of all the senses. When the brain is deprived of one sensory modality, plasticity becomes compensatory: the exception that invalidates the general loss hypothesis giving the opportunity of effective change. Sensory deprivation comes with massive alterations in brain structure and function, behavioral outcomes, and neural interactions. Blind individuals do as good as the sighted and even more, show superior abilities in auditory, tactile and olfactory processing. This behavioral enhancement is accompanied with changes in occipital cortex function, where visual areas at different levels become responsive to non-visual information. The intact senses are in general used more efficiently in the blind but are also used more exclusively. New findings are disentangling these two aspects of compensatory plasticity. What is due to visual deprivation and what is dependent on the extended use of spared modalities? The latter seems to contribute highly to compensatory changes in the congenitally blind. Short-term deprivation through the use of blindfolds shows that cortical excitability of the visual cortex is likely to show rapid modulatory changes after few minutes of light deprivation and therefore changes are possible in adulthood. However, reorganization remains more pronounced in the congenitally blind. Cortico-cortical pathways between visual areas and the areas of preserved sensory modalities are inhibited in the presence of vision, but are unmasked after loss of vision or blindfolding as a mechanism likely to drive cross-modal information to the deafferented visual cortex. The development of specialized higher order visual pathways independently from early sensory experience is likely to preserve their function and switch to the intact modalities. Plasticity in the blind is also accompanied with neurochemical and morphological changes; both intrinsic connectivity and functional coupling at rest are altered but are likewise dependent on different sensory experience and training.

Long intrahemispheric pathways of the human cerebral cortex visualized by dissection (LB21)

Long intrahemispheric pathways of the human cerebral cortex visualized by dissection In order to visualize in the human brain analogous corticocortical pathways linking the parietal and frontal lobes that have been found experimentally in the monkey, we dissected fixed (donated) human hemispheres. Our findings showed four such pathways: Two medial to the corona radiata, and two lateral to the corona radiata. Medial: 1. The fimbria link the hippocampus to the mammillary body. 2. The cingulum bundle connects the medial occipital lobe to the subcallosal cingulate gyrus. Lateral: 3. The uncinate fasciculus links the posterior superior temporal gyrus with the inferior prefrontal cortex. 4. The inferior longitudinal fasciculus connects the anteromedial occipital lobe to the inferior temporal gyrus. We conclude that the posterior cerebral cortex projects heavily to frontal cortex by discrete axonal pathways that connect sensory information to motor mechanisms.

D-serine deficiency attenuates the behavioral and cellular effects induced by the hallucinogenic 5-HT2A receptor agonist DOI

Both the serotonin and glutamate systems have been implicated in the pathophysiology of schizophrenia, as well as in the mechanism of action of antipsychotic drugs. Psychedelic drugs act through the serotonin 2A receptor (5-HT2AR), and elicit a head-twitch response (HTR) in mice, which directly correlates to 5-HT2AR activation and is absent in 5-HT2AR knockout mice. The precise mechanism of this response remains unclear, but both an intrinsic cortico-cortical pathway and a thalamo-cortical pathway involving glutamate release have been proposed. Here, we used a genetic model of NMDAR hypofunction, the serine racemase knockout (SRKO) mouse, to explore the role of glutamatergic transmission in regulating 5-HT2AR-mediated cellular and behavioral responses. SRKO mice treated with the 5-HT2AR agonist (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) showed a clearly diminished HTR and lower induction of c-fos mRNA. These altered functional responses in SRKO mice were not associated with changes in cortical or hippocampal 5-HT levels or in 5-HT2AR and metabotropic glutamate-2 receptor (mGluR2) mRNA and protein expression. Together, these findings suggest that D-serine-dependent NMDAR activity is involved in mediating the cellular and behavioral effects of 5-HT2AR activation.

Neuronal Oscillations in Golgi Cells and Purkinje Cells are Accompanied by Decreases in Shannon Information Entropy

Neuronal oscillations have been shown to contribute to the function of the cerebral cortex by coordinating the neuronal activities of distant cortical regions via a temporal synchronization of neuronal discharge patterns. This can occur regardless whether these regions are linked by cortico-cortical pathways or not. Less is known concerning the role of neuronal oscillations in the cerebellum. Golgi cells and Purkinje cells are both principal cell types in the cerebellum. Purkinje cells are the sole output cells of the cerebellar cortex while Golgi cells contribute to information processing at the input stage of the cerebellar cortex. Both cell types have large cell bodies, as well as dendritic structures, that can generate large currents. The discharge patterns of both these cell types also exhibit oscillations. In view of the massive afferent information conveyed by the mossy fiber-granule cell system to different and distant areas of the cerebellar cortex, it is relevant to inquire the role of cerebellar neuronal oscillations in information processing. In this study, we compared the discharge patterns of Golgi cells and Purkinje cells in conscious rats and in rats anesthetized with urethane. We assessed neuronal oscillations by analyzing the regularity in the timing of individual spikes within a spike train by using autocorrelograms and fast-Fourier transform. We measured the differences in neuronal oscillations and the amount of information content in a spike train (defined by Shannon entropy processed per unit time) in rats under anesthesia and in conscious, awake rats. Our findings indicated that anesthesia caused more prominent neuronal oscillations in both Golgi cells and Purkinje cells accompanied by decreases in Shannon information entropy in their spike trains.