Gonzalo Viana di Prisco - Academia.edu (original) (raw)

Papers by Gonzalo Viana di Prisco

Research paper thumbnail of Informática En El Desarrollo Nacional: Experiencias Y Propuestas Para Venezuela

Research paper thumbnail of Multisite Spike-Field Coherence, Theta Rhythmicity, and Information Flow Within Papez’s Circuit

Neuromethods, Oct 14, 2010

ABSTRACT Understanding the temporal and spectral structure of neural coding with especial attenti... more ABSTRACT Understanding the temporal and spectral structure of neural coding with especial attention to regional specificity and behavioral function is one goal of system neuroscience. Several methodological approaches have been used to analyze signals arising from multisite or distributed probes placed in distant areas to study synchrony and interaction in various species. Neuronal synchronization may be a way to enhance neuronal interactions among neural ensembles but the exact nature of this process remains largely unknown. Spike-field coherence has recently become a popular method when functional integration analysis is being considered for simultaneously collected hybrid signals, such as local field potentials and spike trains. In this chapter, we review some of the most recent approaches and applications of this methodology to address neural circuitry function and behavioral significance. Many authors have contributed extensively to our current understanding of synchronous signals in relation to neural interaction but far more is to occur in future years when both data acquisition and analysis techniques continue to expand. One intriguing and fascinating process to address using these techniques is undoubtedly the hippocampal theta rhythm. Its relevance to brain information processing and behavior makes it both an excellent target process to understand neural states in relation to behavioral significance and a source of physiologically complex integrative signal as many brainstem, diencephalic, and cortical structures appear to contribute to its generation and maintenance. At the end of this chapter, we discuss our own work on neuronal synchronization and resonance within three structures of Papez’s circuit namely, hippocampus, anterior thalamus, and retrosplenial cortex, and discuss its importance for mnemonic function.

Research paper thumbnail of Prenatal Opioid Exposure Impairs Endocannabinoid and Glutamate Transmission in the Dorsal Striatum

ENeuro, Mar 1, 2022

The opioid crisis has contributed to a growing population of children exposed to opioids during f... more The opioid crisis has contributed to a growing population of children exposed to opioids during fetal development; however, many of the long-term effects of opioid exposure on development are unknown. We previously demonstrated that opioids have deleterious effects on endocannabinoid plasticity at glutamate synapses in the dorsal striatum of adolescent rodents, but it is unclear whether prenatal opioid exposure produces similar neuroadaptations. Using a mouse model of prenatal methadone exposure (PME), we performed proteomics, phosphoproteomics, and patch-clamp electrophysiology in the dorsolateral striatum (DLS) and dorsomedial striatum (DMS) to examine synaptic functioning in adolescent PME offspring. PME impacted the proteome and phosphoproteome in a region-and sex-dependent manner. Many proteins and phosphorylated proteins associated with glutamate transmission were differentially abundant in PME offspring, which was associated with reduced glutamate release in the DLS and altered the rise time of excitatory events in the DMS. Similarly, the intrinsic excitability properties of DMS neurons were significantly affected by PME. Last, pathway analyses revealed an enrichment in retrograde endocannabinoid signaling in the DLS, but not in the DMS, of males. Electrophysiology studies confirmed that endocannabinoid-mediated synaptic depression was impaired in the DLS, but not DMS, of PME-males. These results indicate that PME induces persistent neuroadaptations in the dorsal striatum and could contribute to the aberrant behavioral development described in offspring with prenatal opioid exposure.

Research paper thumbnail of Quantitative Investigation of Calcium Signals for Locomotor Pattern Generation in the Lamprey Spinal Cord

Journal of Neurophysiology, Sep 1, 2004

Quantitative investigation of calcium signals for locomotor pattern generation in the lamprey spi... more Quantitative investigation of calcium signals for locomotor pattern generation in the lamprey spinal cord.

Research paper thumbnail of Odor-related bulbar EEG spatial pattern analysis during appetitive conditioning in rabbits

Behavioral Neuroscience, 1985

Research paper thumbnail of Initiation of locomotion in lampreys

Brain Research Reviews, 2008

The spinal circuitry underlying the generation of basic locomotor synergies has been described in... more The spinal circuitry underlying the generation of basic locomotor synergies has been described in substantial detail in lampreys and the cellular mechanisms have been identified. The initiation of locomotion, on the other hand, relies on supraspinal networks and the cellular mechanisms involved are only beginning to be understood. This review examines some of the findings relative to the neural mechanisms involved in the initiation of locomotion of lampreys. Locomotion can be elicited by sensory stimulation or by internal cues associated with fundamental needs of the animal such as food seeking, exploration, and mating. We have described mechanisms by which escape swimming is elicited in lampreys in response to mechanical skin stimulation. A rather simple neural connectivity is involved, including sensory and relay neurons, as well as the brainstem rhombencephalic reticulospinal cells, which act as command neurons. We have shown that reticulospinal cells have intrinsic membrane properties that allow them to transform a short duration sensory input into a long-lasting excitatory command that activates the spinal locomotor networks. These mechanisms constitute an important feature for the activation of escape swimming. Other sensory inputs can also elicit locomotion in lampreys. For instance, we have recently shown that olfactory signals evoke sustained depolarizations in reticulospinal neurons and chemical activation of the olfactory bulbs with local injections of glutamate induces fictive locomotion. The mechanisms by which internal cues initiate locomotion are less understood. Our research has focused on one particular locomotor center in the brainstem, the mesencephalic locomotor region (MLR). The MLR is believed to channel inputs from many brain regions to generate goal-directed locomotion. It activates reticulospinal cells to elicit locomotor output in a graded fashion contrary to escape locomotor bouts, which are all-or-none. MLR inputs to reticulospinal cells use both glutamatergic and cholinergic transmission; nicotinic receptors on reticulospinal cells are involved. MLR excitatory inputs to reticulospinal cells in the middle (MRRN) are larger than those in the posterior rhombencephalic reticular nucleus (PRRN). Moreover at low stimulation strength, reticulospinal cells in the MRRN are activated first, whereas those in

Research paper thumbnail of Theta-rhythmically firing neurons in the anterior thalamus: implications for mnemonic functions of Papez’s circuit

Neuroscience, Jun 1, 2001

Research paper thumbnail of Entrainment of the Spinal Neuronal Network Generating Locomotion

Springer eBooks, 1993

To understand the neural substrate of a behavior such as locomotion we need to know the neural sy... more To understand the neural substrate of a behavior such as locomotion we need to know the neural systems involved, the membrane properties of the neurons generating the behavioral activity pattern, and the interconnections and synaptic interactions among contributing neurons. In this task the best results have been achieved by combining experiments in relatively simple experimental preparations with computer simulations and mathematical analysis of neural models (Grillner et al, 1986; Cohen et al, 1988).

Research paper thumbnail of Author response: The role of anterior insular cortex inputs to dorsolateral striatum in binge alcohol drinking

Research paper thumbnail of The role of anterior insular cortex inputs to dorsolateral striatum in binge alcohol drinking

eLife, Sep 13, 2022

How does binge drinking alcohol change synaptic function, and do these changes maintain binge con... more How does binge drinking alcohol change synaptic function, and do these changes maintain binge consumption? The anterior insular cortex (AIC) and dorsolateral striatum (DLS) are brain regions implicated in alcohol use disorder. In male, but not female mice, we found that binge drinking alcohol produced glutamatergic synaptic adaptations selective to AIC inputs within the DLS. Photoexciting AIC→DLS circuitry in male mice during binge drinking decreased alcohol, but not water consumption and altered alcohol drinking mechanics. Further, drinking mechanics alone from drinking session data predicted alcohol-related circuit changes. AIC→DLS manipulation did not alter operant, valence, or anxiety-related behaviors. These findings suggest that alcohol-mediated changes at AIC inputs govern behavioral sequences that maintain binge drinking and may serve as a circuit-based biomarker for the development of alcohol use disorder. Editor's evaluation Haggerty et al. reported findings examining how changes in brain function are involved in alcohol binge drinking, with a selective focus on the synaptic and circuit alterations that occur in the anterior insular cortex (AIC) inputs within the dorsolateral striatum (DLS). They show that chronic alcohol drinking produces glutamatergic synaptic adaptations in male mice and by stimulating this circuit binge drinking could be reduced without altering either water consumption or general performance for select reinforcing, anxiogenic or locomotor behaviors. The results of this study may specifically improve our understanding of the sex-specific differences in neurocircuitry mediating excessive drinking associated with alcohol use disorder.

Research paper thumbnail of Conditioning of relative frequency of sniffing by rabbits to odors

Journal of Comparative Psychology, 1983

The sniff was identified by a brief episode of increased respiratory rate, usually with a well-de... more The sniff was identified by a brief episode of increased respiratory rate, usually with a well-defined time of onset. It was detected against the background of respiratory activity in rabbits simply, reliably, and noninvasively by statistical evaluation of digitized pneumograph records. The basal rate of exploratory sniffing was controlled by familiarization. Upon conditioning to olfactory cues, the rate of sniffing for CS+ increased sharply above the basal rate during the first 10 trials and was maintained at high levels by continued reinforcement. During extinction with discrimination between olfactory cues, the rate for CS- fell sharply at first and then more slowly toward the basal rate. With pseudoconditioning, the rabbits responded to an unpaired odor after several sessions; the rates of response acquisition and extinction and the maintained level of responding were lower than with a paired odor in classical delayed conditioning, and the response was not discriminative in respect to another novel odor given during extinction. The sniff displayed a prominent sensory bias for olfactory cues. The relative frequencies of sniffing and respiratory slowing were measured as conditioned responses by screening procedures with a small computer.

Research paper thumbnail of Cellular Network Underlying Locomotion as Revealed in a Lower Vertebrate Model: Transmitters, Membrane Properties, Circuitry, and Simulation

Cold Spring Harbor Symposia on Quantitative Biology, 1990

Research paper thumbnail of 5-HT innervation of reticulospinal neurons and other brainstem structures in lamprey

Journal of comparative neurology, Apr 1, 1994

In order to determine if reticulospinal neurons involved in the control of locomotion and respons... more In order to determine if reticulospinal neurons involved in the control of locomotion and responsive to exogenously applied 5-hydroxtryptamine (5-HT) are innervated by fibers that contain serotonin, the serotoninergic innervation of reticulospinal neurons, identified by retrograde labeling with fluorescein-conjugated dextran-amine (FDA), was investigated by immunohistochemistry in the lamprey brainstem. A widespread distribution of 5-HT immunoreactive (5-HT-ir) fibers was seen within the basal plate of the brainstem, an area containing reticulospinal somata and dendritic arborizations. Numerous 5-HT varicose fibers were found in close relation to large reticulospinal cell bodies, particularly in the middle and anterior rhombencephalic reticular nuclei (MRRN and ARRN). Some of these reticulospinal somata were surrounded by a very dense pericellular 5-HT innervation. 5-HT-ir fibers were also seen in other brain structures that are known to influence reticulospinal neurons such as the rhombencephalic alar plate containing sensory relay interneurons, cranial nerves (111-X), cerebellum, and tectum. These findings suggest that, as in the spinal cord, motor behavior controlled by reticulospinal neurons may be subject to a serotoninergic modulation.

Research paper thumbnail of Hebb synaptic plasticity

Progress in Neurobiology, 1984

Contents I. Introduction 89 2. What are Hebb synapses? 91 3. Is visual cortical development expla... more Contents I. Introduction 89 2. What are Hebb synapses? 91 3. Is visual cortical development explained by hebbian synapses? 92 3.1. Synaptic competition 92 3.2. Selective vs instructive mechanisms 93 4. Hebb plasticity in neural systems 94 4.1. Cerebellar learning 94 4.2. Hippocampal LTP 95 5. Cellular associative learning: The evidence in identified synapses 96 6. Conclusions 97 Acknowledgements 98 References 98

Research paper thumbnail of Classification of EEG Spatial Patterns with a Tree-Structured Methodology: CART

IEEE Transactions on Biomedical Engineering, Dec 1, 1986

The increasing use of computers in statistics has spawned a new generation of multivariate statis... more The increasing use of computers in statistics has spawned a new generation of multivariate statistical techniques. Chief among these is a tree-structured approach to classification and regression analysis. The CART, or Classification and Regression Trees, program implements a recursive partitioning procedure based on an iterative search for best binary "splits" of data. Resultant classifiers consist of binary trees whose leaves determine class labeling. Extensive use of data resampling techniques replaces biased classifier performance measures. Here, tree-structured methodology and data resampling techniques are reviewed. A case study emphasizes the use of CART in data exploration and classification. The data consist of spatial patterns of EEG recorded from the olfactory bulb of rabbits. CART is used to confirm previous pattern analyses and to show that odor-specificity of EEG lies in a spatially modulated amplitude pattern of a global waveform. To our knowledge, this is the first report of the application of an explicitly tree-structured methodology to classification of spatial patterns of EEG activity.

Research paper thumbnail of Anterior thalamic unit discharge profiles and coherence with hippocampal theta rhythm

Thalamus and Related Systems, Apr 1, 2003

The anterior thalamus (ATh) is a key structure of the limbic system and serves a direct role in s... more The anterior thalamus (ATh) is a key structure of the limbic system and serves a direct role in spatial memory. We examined the discharge properties of neurons of the anterior thalamus during states of the hippocampal electroencephalogram (theta and non-theta states). Units were recorded in the anteroventral (AV, n = 96), the anterodorsal (AD, n = 44) and the anteromedial (AM, n = 48) nuclei of the thalamus. The majority of theta-related cells fired at higher rates in the presence than absence of theta (theta-on cells); while a small percentage (∼13%) discharge at reduced rates with theta (theta-off cells). Theta-off cells were found in AD and AM but not in AV. Mean discharge rates for theta-on cells during control and theta conditions were 6.0 ± 0.52 and 14.48 ± 0.96 Hz for AV cells; 4.43 ± 1.25 and 10.05 ± 1.28 Hz for AD cells, and 2.60 ± 0.3 and 6.42 ± 0.9 Hz for AM cells. Approximately 40% of AV cells, 21.9% of AD units, and 5.7% of AM cells discharged rhythmically, synchronous with the theta rhythm. A subpopulation of ATh cells fired slightly rhythmicity, but with activity strongly phase-locked to EEG oscillations in the crosscorrelogram, indicating a modulation at theta frequency. Cells were classified as: rhythmic (R), non-rhythmic (N), and intermediate (I) based on quantitative criteria. About 75% of theta-on cells (i.e. R and I cells) showed significant coherence with theta. These cells were distributed throughout the extent of the anterior thalamus. The present findings of theta rhythmic cells in the anterior thalamus, together with previous demonstrations of 'theta' cells in other structures of Papez's circuit, suggests that a theta rhythmic signal may reverberate throughout the circuit, possibly involved in memory processing functions of this limbic network.

Research paper thumbnail of Trigeminal inputs to reticulospinal neurones in lampreys are mediated by excitatory and inhibitory amino acids

Brain Research, Oct 1, 1995

Reticulospinal (RS) neurones integrate sensory inputs from several modalities to generate appropr... more Reticulospinal (RS) neurones integrate sensory inputs from several modalities to generate appropriate motor commands for maintaining body orientation and initiation of locomotion in lampreys. As in other vertebrates, trigeminal afferents convey sensory inputs from the head region. The in vitro brainstem/spinal cord preparation of the lamprey was used for characterizing trigeminal inputs neurones as well as the transmitter systems involved. The trigeminal nerve on each side was electrically stimulated and sy responses, which consisted of mixed excitation and inhibition, were recorded intracellularly in the middle and posterior rh reticular nuclei. The EPSPs were mediated by activation of cu-amino-3-hydroxy-5-methyl-Gsoxazolepropionic acid (A receptors, An increase in the Iate phase of the excitatory response occurred when Mg"+ ions were removed from the Ringer's solution. This effect was antagonized by 2-amino-S-phosphonopentanoate (2-APS) or reversed by restoring Mg"+ ions to the perfusate suggesting the activation of NWmethyl-a-aspartate (NMDA) receptors. IPSPs were mediated by glycine, These findings are similar to those reported far other types of sensory inputs conveyed to RS ncurones, where excitatory and inhibitory amino acid transmission is also involved.

Research paper thumbnail of Impact of <i>Phospholipase C Gamma 2</i> Alzheimer's Disease Variants on Microglial Biology and Disease Pathogenesis

Alzheimers & Dementia, Dec 1, 2022

BackgroundAlzheimer’s disease (AD) and other neurodegenerative diseases are typified by a robust ... more BackgroundAlzheimer’s disease (AD) and other neurodegenerative diseases are typified by a robust microglial‐mediated immune response. Phospholipase C gamma 2 (PLCG2), whose variants confer altered risk for AD, is a critical signaling element for various immune receptors and is a key regulatory hub gene for immune signaling. A functional hypermorphic P522R variant (rs72824905) of PLCG2 has been identified to be protective against AD (OR= 0.68, p=5.83‐10). Significantly, we identified a novel SNP (rs617749044) associated with elevated AD risk (OR=1.164; p=0.047) encoding the PLCG2 M28L variant.MethodTo investigate the impact of PLCG2 AD risk variants on microglial biology and disease pathogenesis, we have generated mice bearing either the M28L risk or the P522R protective PLCG2 variant, all crossed onto the 5XFAD amyloidogenic murine model of AD.ResultHere, we provide comprehensive analysis of PLCG2 action in mouse models of AD. We demonstrate that PLCG2 variants regulate protein‐protein interaction, alter microglial phenotypes in 5XFAD mice, regulate cytokine levels, drive distinct transcriptional phenotypes of microglia, and affect plaque pathology. Our data demonstrate that the M28L variant results in accelerated and exacerbated disease‐related pathology, and conversely, the P522R variant appeared to attenuate disease severity and progression.ConclusionTogether, our finding provides evidence that PLCG2 play an important role in AD pathophysiology, indicating PLCG2 as a potential new therapeutic target for AD.

Research paper thumbnail of Signals from posterior parietal area 5 to motor cortex during locomotion

Cerebral Cortex, Apr 5, 2022

Area 5 of the parietal cortex is part of the "dorsal stream" cortical pathway which processes vis... more Area 5 of the parietal cortex is part of the "dorsal stream" cortical pathway which processes visual information for action. The signals that area 5 ultimately conveys to motor cortex, the main area providing output to the spinal cord, are unknown. We analyzed area 5 neuronal activity during vision-independent locomotion on a f lat surface and vision-dependent locomotion on a horizontal ladder in cats focusing on corticocortical neurons (CCs) projecting to motor cortex from the upper and deeper cortical layers and compared it to that of neighboring unidentified neurons (noIDs). We found that upon transition from vision-independent to vision-dependent locomotion, the low discharge of CCs in layer V doubled and the proportion of cells with 2 bursts per stride tended to increase. In layer V, the group of 2-bursters developed 2 activity peaks that coincided with peaks of gaze shifts along the surface away from the animal, described previously. One-bursters and either subpopulation in supragranular layers did not transmit any clear unified stride-related signal to the motor cortex. Most CC group activities did not mirror those of their noID counterparts. CCs with receptive fields on the shoulder, elbow, or wrist/paw discharged in opposite phases with the respective groups of pyramidal tract neurons of motor cortex, the cortico-spinal cells.

Research paper thumbnail of 5-Hydroxytryptamine modulates spike frequency regulation in reticulospinal neurons involved in the control of locomotion in lamprey

Neuroscience Letters, 1992

Research paper thumbnail of Informática En El Desarrollo Nacional: Experiencias Y Propuestas Para Venezuela

Research paper thumbnail of Multisite Spike-Field Coherence, Theta Rhythmicity, and Information Flow Within Papez’s Circuit

Neuromethods, Oct 14, 2010

ABSTRACT Understanding the temporal and spectral structure of neural coding with especial attenti... more ABSTRACT Understanding the temporal and spectral structure of neural coding with especial attention to regional specificity and behavioral function is one goal of system neuroscience. Several methodological approaches have been used to analyze signals arising from multisite or distributed probes placed in distant areas to study synchrony and interaction in various species. Neuronal synchronization may be a way to enhance neuronal interactions among neural ensembles but the exact nature of this process remains largely unknown. Spike-field coherence has recently become a popular method when functional integration analysis is being considered for simultaneously collected hybrid signals, such as local field potentials and spike trains. In this chapter, we review some of the most recent approaches and applications of this methodology to address neural circuitry function and behavioral significance. Many authors have contributed extensively to our current understanding of synchronous signals in relation to neural interaction but far more is to occur in future years when both data acquisition and analysis techniques continue to expand. One intriguing and fascinating process to address using these techniques is undoubtedly the hippocampal theta rhythm. Its relevance to brain information processing and behavior makes it both an excellent target process to understand neural states in relation to behavioral significance and a source of physiologically complex integrative signal as many brainstem, diencephalic, and cortical structures appear to contribute to its generation and maintenance. At the end of this chapter, we discuss our own work on neuronal synchronization and resonance within three structures of Papez’s circuit namely, hippocampus, anterior thalamus, and retrosplenial cortex, and discuss its importance for mnemonic function.

Research paper thumbnail of Prenatal Opioid Exposure Impairs Endocannabinoid and Glutamate Transmission in the Dorsal Striatum

ENeuro, Mar 1, 2022

The opioid crisis has contributed to a growing population of children exposed to opioids during f... more The opioid crisis has contributed to a growing population of children exposed to opioids during fetal development; however, many of the long-term effects of opioid exposure on development are unknown. We previously demonstrated that opioids have deleterious effects on endocannabinoid plasticity at glutamate synapses in the dorsal striatum of adolescent rodents, but it is unclear whether prenatal opioid exposure produces similar neuroadaptations. Using a mouse model of prenatal methadone exposure (PME), we performed proteomics, phosphoproteomics, and patch-clamp electrophysiology in the dorsolateral striatum (DLS) and dorsomedial striatum (DMS) to examine synaptic functioning in adolescent PME offspring. PME impacted the proteome and phosphoproteome in a region-and sex-dependent manner. Many proteins and phosphorylated proteins associated with glutamate transmission were differentially abundant in PME offspring, which was associated with reduced glutamate release in the DLS and altered the rise time of excitatory events in the DMS. Similarly, the intrinsic excitability properties of DMS neurons were significantly affected by PME. Last, pathway analyses revealed an enrichment in retrograde endocannabinoid signaling in the DLS, but not in the DMS, of males. Electrophysiology studies confirmed that endocannabinoid-mediated synaptic depression was impaired in the DLS, but not DMS, of PME-males. These results indicate that PME induces persistent neuroadaptations in the dorsal striatum and could contribute to the aberrant behavioral development described in offspring with prenatal opioid exposure.

Research paper thumbnail of Quantitative Investigation of Calcium Signals for Locomotor Pattern Generation in the Lamprey Spinal Cord

Journal of Neurophysiology, Sep 1, 2004

Quantitative investigation of calcium signals for locomotor pattern generation in the lamprey spi... more Quantitative investigation of calcium signals for locomotor pattern generation in the lamprey spinal cord.

Research paper thumbnail of Odor-related bulbar EEG spatial pattern analysis during appetitive conditioning in rabbits

Behavioral Neuroscience, 1985

Research paper thumbnail of Initiation of locomotion in lampreys

Brain Research Reviews, 2008

The spinal circuitry underlying the generation of basic locomotor synergies has been described in... more The spinal circuitry underlying the generation of basic locomotor synergies has been described in substantial detail in lampreys and the cellular mechanisms have been identified. The initiation of locomotion, on the other hand, relies on supraspinal networks and the cellular mechanisms involved are only beginning to be understood. This review examines some of the findings relative to the neural mechanisms involved in the initiation of locomotion of lampreys. Locomotion can be elicited by sensory stimulation or by internal cues associated with fundamental needs of the animal such as food seeking, exploration, and mating. We have described mechanisms by which escape swimming is elicited in lampreys in response to mechanical skin stimulation. A rather simple neural connectivity is involved, including sensory and relay neurons, as well as the brainstem rhombencephalic reticulospinal cells, which act as command neurons. We have shown that reticulospinal cells have intrinsic membrane properties that allow them to transform a short duration sensory input into a long-lasting excitatory command that activates the spinal locomotor networks. These mechanisms constitute an important feature for the activation of escape swimming. Other sensory inputs can also elicit locomotion in lampreys. For instance, we have recently shown that olfactory signals evoke sustained depolarizations in reticulospinal neurons and chemical activation of the olfactory bulbs with local injections of glutamate induces fictive locomotion. The mechanisms by which internal cues initiate locomotion are less understood. Our research has focused on one particular locomotor center in the brainstem, the mesencephalic locomotor region (MLR). The MLR is believed to channel inputs from many brain regions to generate goal-directed locomotion. It activates reticulospinal cells to elicit locomotor output in a graded fashion contrary to escape locomotor bouts, which are all-or-none. MLR inputs to reticulospinal cells use both glutamatergic and cholinergic transmission; nicotinic receptors on reticulospinal cells are involved. MLR excitatory inputs to reticulospinal cells in the middle (MRRN) are larger than those in the posterior rhombencephalic reticular nucleus (PRRN). Moreover at low stimulation strength, reticulospinal cells in the MRRN are activated first, whereas those in

Research paper thumbnail of Theta-rhythmically firing neurons in the anterior thalamus: implications for mnemonic functions of Papez’s circuit

Neuroscience, Jun 1, 2001

Research paper thumbnail of Entrainment of the Spinal Neuronal Network Generating Locomotion

Springer eBooks, 1993

To understand the neural substrate of a behavior such as locomotion we need to know the neural sy... more To understand the neural substrate of a behavior such as locomotion we need to know the neural systems involved, the membrane properties of the neurons generating the behavioral activity pattern, and the interconnections and synaptic interactions among contributing neurons. In this task the best results have been achieved by combining experiments in relatively simple experimental preparations with computer simulations and mathematical analysis of neural models (Grillner et al, 1986; Cohen et al, 1988).

Research paper thumbnail of Author response: The role of anterior insular cortex inputs to dorsolateral striatum in binge alcohol drinking

Research paper thumbnail of The role of anterior insular cortex inputs to dorsolateral striatum in binge alcohol drinking

eLife, Sep 13, 2022

How does binge drinking alcohol change synaptic function, and do these changes maintain binge con... more How does binge drinking alcohol change synaptic function, and do these changes maintain binge consumption? The anterior insular cortex (AIC) and dorsolateral striatum (DLS) are brain regions implicated in alcohol use disorder. In male, but not female mice, we found that binge drinking alcohol produced glutamatergic synaptic adaptations selective to AIC inputs within the DLS. Photoexciting AIC→DLS circuitry in male mice during binge drinking decreased alcohol, but not water consumption and altered alcohol drinking mechanics. Further, drinking mechanics alone from drinking session data predicted alcohol-related circuit changes. AIC→DLS manipulation did not alter operant, valence, or anxiety-related behaviors. These findings suggest that alcohol-mediated changes at AIC inputs govern behavioral sequences that maintain binge drinking and may serve as a circuit-based biomarker for the development of alcohol use disorder. Editor's evaluation Haggerty et al. reported findings examining how changes in brain function are involved in alcohol binge drinking, with a selective focus on the synaptic and circuit alterations that occur in the anterior insular cortex (AIC) inputs within the dorsolateral striatum (DLS). They show that chronic alcohol drinking produces glutamatergic synaptic adaptations in male mice and by stimulating this circuit binge drinking could be reduced without altering either water consumption or general performance for select reinforcing, anxiogenic or locomotor behaviors. The results of this study may specifically improve our understanding of the sex-specific differences in neurocircuitry mediating excessive drinking associated with alcohol use disorder.

Research paper thumbnail of Conditioning of relative frequency of sniffing by rabbits to odors

Journal of Comparative Psychology, 1983

The sniff was identified by a brief episode of increased respiratory rate, usually with a well-de... more The sniff was identified by a brief episode of increased respiratory rate, usually with a well-defined time of onset. It was detected against the background of respiratory activity in rabbits simply, reliably, and noninvasively by statistical evaluation of digitized pneumograph records. The basal rate of exploratory sniffing was controlled by familiarization. Upon conditioning to olfactory cues, the rate of sniffing for CS+ increased sharply above the basal rate during the first 10 trials and was maintained at high levels by continued reinforcement. During extinction with discrimination between olfactory cues, the rate for CS- fell sharply at first and then more slowly toward the basal rate. With pseudoconditioning, the rabbits responded to an unpaired odor after several sessions; the rates of response acquisition and extinction and the maintained level of responding were lower than with a paired odor in classical delayed conditioning, and the response was not discriminative in respect to another novel odor given during extinction. The sniff displayed a prominent sensory bias for olfactory cues. The relative frequencies of sniffing and respiratory slowing were measured as conditioned responses by screening procedures with a small computer.

Research paper thumbnail of Cellular Network Underlying Locomotion as Revealed in a Lower Vertebrate Model: Transmitters, Membrane Properties, Circuitry, and Simulation

Cold Spring Harbor Symposia on Quantitative Biology, 1990

Research paper thumbnail of 5-HT innervation of reticulospinal neurons and other brainstem structures in lamprey

Journal of comparative neurology, Apr 1, 1994

In order to determine if reticulospinal neurons involved in the control of locomotion and respons... more In order to determine if reticulospinal neurons involved in the control of locomotion and responsive to exogenously applied 5-hydroxtryptamine (5-HT) are innervated by fibers that contain serotonin, the serotoninergic innervation of reticulospinal neurons, identified by retrograde labeling with fluorescein-conjugated dextran-amine (FDA), was investigated by immunohistochemistry in the lamprey brainstem. A widespread distribution of 5-HT immunoreactive (5-HT-ir) fibers was seen within the basal plate of the brainstem, an area containing reticulospinal somata and dendritic arborizations. Numerous 5-HT varicose fibers were found in close relation to large reticulospinal cell bodies, particularly in the middle and anterior rhombencephalic reticular nuclei (MRRN and ARRN). Some of these reticulospinal somata were surrounded by a very dense pericellular 5-HT innervation. 5-HT-ir fibers were also seen in other brain structures that are known to influence reticulospinal neurons such as the rhombencephalic alar plate containing sensory relay interneurons, cranial nerves (111-X), cerebellum, and tectum. These findings suggest that, as in the spinal cord, motor behavior controlled by reticulospinal neurons may be subject to a serotoninergic modulation.

Research paper thumbnail of Hebb synaptic plasticity

Progress in Neurobiology, 1984

Contents I. Introduction 89 2. What are Hebb synapses? 91 3. Is visual cortical development expla... more Contents I. Introduction 89 2. What are Hebb synapses? 91 3. Is visual cortical development explained by hebbian synapses? 92 3.1. Synaptic competition 92 3.2. Selective vs instructive mechanisms 93 4. Hebb plasticity in neural systems 94 4.1. Cerebellar learning 94 4.2. Hippocampal LTP 95 5. Cellular associative learning: The evidence in identified synapses 96 6. Conclusions 97 Acknowledgements 98 References 98

Research paper thumbnail of Classification of EEG Spatial Patterns with a Tree-Structured Methodology: CART

IEEE Transactions on Biomedical Engineering, Dec 1, 1986

The increasing use of computers in statistics has spawned a new generation of multivariate statis... more The increasing use of computers in statistics has spawned a new generation of multivariate statistical techniques. Chief among these is a tree-structured approach to classification and regression analysis. The CART, or Classification and Regression Trees, program implements a recursive partitioning procedure based on an iterative search for best binary "splits" of data. Resultant classifiers consist of binary trees whose leaves determine class labeling. Extensive use of data resampling techniques replaces biased classifier performance measures. Here, tree-structured methodology and data resampling techniques are reviewed. A case study emphasizes the use of CART in data exploration and classification. The data consist of spatial patterns of EEG recorded from the olfactory bulb of rabbits. CART is used to confirm previous pattern analyses and to show that odor-specificity of EEG lies in a spatially modulated amplitude pattern of a global waveform. To our knowledge, this is the first report of the application of an explicitly tree-structured methodology to classification of spatial patterns of EEG activity.

Research paper thumbnail of Anterior thalamic unit discharge profiles and coherence with hippocampal theta rhythm

Thalamus and Related Systems, Apr 1, 2003

The anterior thalamus (ATh) is a key structure of the limbic system and serves a direct role in s... more The anterior thalamus (ATh) is a key structure of the limbic system and serves a direct role in spatial memory. We examined the discharge properties of neurons of the anterior thalamus during states of the hippocampal electroencephalogram (theta and non-theta states). Units were recorded in the anteroventral (AV, n = 96), the anterodorsal (AD, n = 44) and the anteromedial (AM, n = 48) nuclei of the thalamus. The majority of theta-related cells fired at higher rates in the presence than absence of theta (theta-on cells); while a small percentage (∼13%) discharge at reduced rates with theta (theta-off cells). Theta-off cells were found in AD and AM but not in AV. Mean discharge rates for theta-on cells during control and theta conditions were 6.0 ± 0.52 and 14.48 ± 0.96 Hz for AV cells; 4.43 ± 1.25 and 10.05 ± 1.28 Hz for AD cells, and 2.60 ± 0.3 and 6.42 ± 0.9 Hz for AM cells. Approximately 40% of AV cells, 21.9% of AD units, and 5.7% of AM cells discharged rhythmically, synchronous with the theta rhythm. A subpopulation of ATh cells fired slightly rhythmicity, but with activity strongly phase-locked to EEG oscillations in the crosscorrelogram, indicating a modulation at theta frequency. Cells were classified as: rhythmic (R), non-rhythmic (N), and intermediate (I) based on quantitative criteria. About 75% of theta-on cells (i.e. R and I cells) showed significant coherence with theta. These cells were distributed throughout the extent of the anterior thalamus. The present findings of theta rhythmic cells in the anterior thalamus, together with previous demonstrations of 'theta' cells in other structures of Papez's circuit, suggests that a theta rhythmic signal may reverberate throughout the circuit, possibly involved in memory processing functions of this limbic network.

Research paper thumbnail of Trigeminal inputs to reticulospinal neurones in lampreys are mediated by excitatory and inhibitory amino acids

Brain Research, Oct 1, 1995

Reticulospinal (RS) neurones integrate sensory inputs from several modalities to generate appropr... more Reticulospinal (RS) neurones integrate sensory inputs from several modalities to generate appropriate motor commands for maintaining body orientation and initiation of locomotion in lampreys. As in other vertebrates, trigeminal afferents convey sensory inputs from the head region. The in vitro brainstem/spinal cord preparation of the lamprey was used for characterizing trigeminal inputs neurones as well as the transmitter systems involved. The trigeminal nerve on each side was electrically stimulated and sy responses, which consisted of mixed excitation and inhibition, were recorded intracellularly in the middle and posterior rh reticular nuclei. The EPSPs were mediated by activation of cu-amino-3-hydroxy-5-methyl-Gsoxazolepropionic acid (A receptors, An increase in the Iate phase of the excitatory response occurred when Mg"+ ions were removed from the Ringer's solution. This effect was antagonized by 2-amino-S-phosphonopentanoate (2-APS) or reversed by restoring Mg"+ ions to the perfusate suggesting the activation of NWmethyl-a-aspartate (NMDA) receptors. IPSPs were mediated by glycine, These findings are similar to those reported far other types of sensory inputs conveyed to RS ncurones, where excitatory and inhibitory amino acid transmission is also involved.

Research paper thumbnail of Impact of <i>Phospholipase C Gamma 2</i> Alzheimer's Disease Variants on Microglial Biology and Disease Pathogenesis

Alzheimers & Dementia, Dec 1, 2022

BackgroundAlzheimer’s disease (AD) and other neurodegenerative diseases are typified by a robust ... more BackgroundAlzheimer’s disease (AD) and other neurodegenerative diseases are typified by a robust microglial‐mediated immune response. Phospholipase C gamma 2 (PLCG2), whose variants confer altered risk for AD, is a critical signaling element for various immune receptors and is a key regulatory hub gene for immune signaling. A functional hypermorphic P522R variant (rs72824905) of PLCG2 has been identified to be protective against AD (OR= 0.68, p=5.83‐10). Significantly, we identified a novel SNP (rs617749044) associated with elevated AD risk (OR=1.164; p=0.047) encoding the PLCG2 M28L variant.MethodTo investigate the impact of PLCG2 AD risk variants on microglial biology and disease pathogenesis, we have generated mice bearing either the M28L risk or the P522R protective PLCG2 variant, all crossed onto the 5XFAD amyloidogenic murine model of AD.ResultHere, we provide comprehensive analysis of PLCG2 action in mouse models of AD. We demonstrate that PLCG2 variants regulate protein‐protein interaction, alter microglial phenotypes in 5XFAD mice, regulate cytokine levels, drive distinct transcriptional phenotypes of microglia, and affect plaque pathology. Our data demonstrate that the M28L variant results in accelerated and exacerbated disease‐related pathology, and conversely, the P522R variant appeared to attenuate disease severity and progression.ConclusionTogether, our finding provides evidence that PLCG2 play an important role in AD pathophysiology, indicating PLCG2 as a potential new therapeutic target for AD.

Research paper thumbnail of Signals from posterior parietal area 5 to motor cortex during locomotion

Cerebral Cortex, Apr 5, 2022

Area 5 of the parietal cortex is part of the "dorsal stream" cortical pathway which processes vis... more Area 5 of the parietal cortex is part of the "dorsal stream" cortical pathway which processes visual information for action. The signals that area 5 ultimately conveys to motor cortex, the main area providing output to the spinal cord, are unknown. We analyzed area 5 neuronal activity during vision-independent locomotion on a f lat surface and vision-dependent locomotion on a horizontal ladder in cats focusing on corticocortical neurons (CCs) projecting to motor cortex from the upper and deeper cortical layers and compared it to that of neighboring unidentified neurons (noIDs). We found that upon transition from vision-independent to vision-dependent locomotion, the low discharge of CCs in layer V doubled and the proportion of cells with 2 bursts per stride tended to increase. In layer V, the group of 2-bursters developed 2 activity peaks that coincided with peaks of gaze shifts along the surface away from the animal, described previously. One-bursters and either subpopulation in supragranular layers did not transmit any clear unified stride-related signal to the motor cortex. Most CC group activities did not mirror those of their noID counterparts. CCs with receptive fields on the shoulder, elbow, or wrist/paw discharged in opposite phases with the respective groups of pyramidal tract neurons of motor cortex, the cortico-spinal cells.

Research paper thumbnail of 5-Hydroxytryptamine modulates spike frequency regulation in reticulospinal neurons involved in the control of locomotion in lamprey

Neuroscience Letters, 1992