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1.
Behav Pharmacol ; 35(2-3): 79-91, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38451022

ABSTRACT

Remarkable performance improvements occur at the end of the third postnatal week in rodents tested in various tasks that require navigation according to spatial context. While alterations in hippocampal function at least partially subserve this cognitive advancement, physiological explanations remain incomplete. Previously, we discovered that developmental modifications to hippocampal glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in juvenile rats was related to more mature spontaneous alternation behavior in a symmetrical Y-maze. Moreover, a positive allosteric modulator of AMPA receptors enabled immature rats to alternate at rates seen in older animals, suggesting an excitatory synaptic limitation to hippocampal maturation. We then validated the Barnes maze for juvenile rats in order to test the effects of positive AMPA receptor modulation on a goal-directed spatial memory task. Here we report the effects of the AMPA receptor modulator, CX614, on spatial learning and memory in the Barnes maze. Similar to our prior report, animals just over 3 weeks of age display substantial improvements in learning and memory performance parameters compared to animals just under 3 weeks of age. A moderate dose of CX614 enabled immature animals to move more directly to the goal location, but only after 1 day of training. This performance improvement was observed on the second day of training with drug delivery or during a memory probe trial performed without drug delivery after the second day of training. Higher doses created more search errors, especially in more mature animals. Overall, CX614 provided modest performance benefits for immature rats in a goal-directed spatial memory task.


Subject(s)
Receptors, AMPA , Spatial Learning , Rats , Animals , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology , Spatial Memory , Cognition
2.
Aerosp Med Hum Perform ; 95(1): 54-58, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38158567

ABSTRACT

INTRODUCTION: Exposure to high ambient altitudes above 10,000 ft (3048 m) over sea level during aviation can present the risk of hypobaric hypoxia. Hypoxia can impair sensory and cognitive functions, degrading performance and leading to mishaps. Military aircrew undergo regular hypoxia familiarization training to recognize their symptoms and understand the consequences of hypoxia. However, over the years, aviators have come to believe that individuals have a "personal hypoxia signature." The idea is that intraindividual variability in symptom experience during repeated exposure is low. In other words, individuals will experience the same symptoms during hypoxia from day to day, year to year.METHODS: We critically reviewed the existing literature on this hypothesis. Most studies that claim to support the notion of a signature only examine group-level data, which do not inform individual-level consistency. Other studies use inappropriate statistical methods, while still others do not control for accuracy of recall over the period of years. To combat these shortcomings, we present a dataset of 91 individuals who completed nearly identical mask-off, normobaric hypoxia exposures days apart.RESULTS: We found that for every symptom on the Hypoxia Symptom Questionnaire, at least half of the subjects reported the symptom inconsistently across repeated exposure. This means that, at best, 50% of subjects did not report the same symptom across exposures.DISCUSSION: These data provide compelling evidence against the existence of hypoxia signatures. We urge that hypoxia familiarization training incorporate these findings and encourage individuals to expect a wide range of hypoxia symptoms upon repeated exposure.Cox BD, McHail DG, Blacker KJ. Personal hypoxia symptoms vary widely within individuals. Aerosp Med Hum Perform. 2024; 95(1):54-58.


Subject(s)
Aerospace Medicine , Aviation , Humans , Altitude , Hypoxia/diagnosis , Surveys and Questionnaires
3.
Front Neurosci ; 16: 846001, 2022.
Article in English | MEDLINE | ID: mdl-35546885

ABSTRACT

Reduced levels of environmental oxygen lead to hypoxic hypoxia and are a primary threat in tactical aviation. The visual system is particularly vulnerable to hypoxia, and its impairment can severely impact performance. The auditory system is relatively spared by hypoxia, although which stages of auditory processing are most impacted by hypoxia remains unclear. Previous work has used electroencephalography (EEG) to assess neural markers of cognitive processing for visual and auditory stimuli and found that these markers were sensitive to a normobaric hypoxic exposure. In the current study, we assessed whether early sensory evoked potentials, that precede cognitive activity, are also impaired by normobaric hypoxia. In a within-subjects design, we compared visual (P100) and auditory evoked potentials (sensory gating for the P50, N100, and P200) in 34 healthy adults during normoxic (21% O2) and two separate hypoxic (9.7% O2) exposures. Self-reported symptoms of hypoxia were also assessed using the Hypoxia Symptom Questionnaire (HSQ). We found that P100 mean amplitude was not reduced under hypoxic compared to normoxic conditions, suggesting no statistically significant impairment of early visual processing. The sensory gating ratio for auditory stimuli was intact for paired responses of the P50 and N100. However, the P200 sensory gating ratio was attenuated under hypoxic compared to normoxic conditions, suggesting disruption of the auditory system specific to the level of allocating attention that follows basic auditory processing. Exploratory analyses of HSQ scores identified a robust effect of hypoxia. However, consistency of symptoms reported between the two hypoxia exposures exhibited high intra-individual variability, which may have implications for the theory that individuals have a consistent hypoxia signature or reliable constellation of responses to hypoxia. These findings suggest that early sensory processing is not impaired during hypoxia, but for the auditory system there is impairment at the level of attentional processing. Given the previous findings of impaired visual performance under hypoxia, these results suggest that this impairment does not stem from early visual processing deficits in visual cortex. Together these findings help focus the search on when and where hypoxia-induced deficits occur and may guide the development of countermeasures for hypoxia in tactical aviation.

4.
Physiol Behav ; 239: 113508, 2021 10 01.
Article in English | MEDLINE | ID: mdl-34175363

ABSTRACT

Exposure to reduced levels of breathable oxygen is known to cause a number of deleterious effects on human performance. Previous work has demonstrated that in healthy adults, hypoxia results in decrements on a wide range of sensory, cognitive, and motor tasks. However, very little is known about the time course of recovery of cognitive functions following a hypoxic exposure. While previous studies have shown that physiological responses like heart rate and oxygen saturation rebound almost immediately, one previous study has shown a delayed recovery for response time (RT) measures following hypoxia. In the current study, we assessed the time course of neurocognitive recovery following a hypoxic exposure in healthy adults using the psychomotor vigilance task (PVT), passively elicited event-related potentials (ERPs) that assess auditory processing, and physiological measures. We also compared whether speed of recovery differed when participants were provided with 21% or 100% oxygen immediately following hypoxic exposure. Participants underwent a baseline testing session and two separate recovery sessions where they were assessed during a hypoxic exposure and at regular intervals for up to four hours post-exposure. Results demonstrated that RT, as measured by the PVT, significantly slowed during hypoxia compared to baseline and continued to be impaired until 60 min post-exposure. We assessed the mismatch negativity (MMN) and P3a ERP components in response to an auditory oddball paradigm and found a significant reduction in the amplitude of the MMN during hypoxia compared to baseline and that attenuation in amplitude persisted for up to 120 min post-exposure. Together, these results indicate that both RT and auditory processing showed a delayed recovery following hypoxia. We found no strong evidence for differential recovery speed based on recovery gas administered (21% versus 100% oxygen). These results have implications for guidance regarding return-to-duty status for military aviators following a hypoxic exposure.


Subject(s)
Electroencephalography , Evoked Potentials , Adult , Cognition , Evoked Potentials, Auditory , Humans , Hypoxia , Reaction Time
5.
Front Cell Dev Biol ; 9: 621308, 2021.
Article in English | MEDLINE | ID: mdl-33816470

ABSTRACT

Severe early life stress has long been associated with neuropsychological disorders in adulthood, including depression, schizophrenia, post-traumatic stress disorder, and memory dysfunction. To some extent, all of these conditions involve dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and reduced negative feedback inhibition of cortisol release in adulthood. However, the time course for mental health and hormonal outcomes across life stages and the attributes of early life stress that direct the behavioral and biological alterations is not fully understood. We designed our studies to compare outcomes of the two most common maternal deprivation schedules on cognitive ability prior to adulthood. We exposed rat pups to daily or randomly spaced maternal separation bouts within the first 3 weeks of life and examined cognitive performance, neurotrophic signaling, and stress and immune system markers during puberty. We found that the daily separation schedule impaired spatial learning while the randomly spaced schedule did not alter maze performance relative to normally reared control animals. Animals that underwent daily separation showed a tendency for reduced body weight compared to the randomly spaced condition, but there were no differences in adrenal weight. Thymus weight normalized by body weight was increased following daily separation compared to random separation and control conditions. Plasma corticosterone levels measured after behavior testing did not differ amongst experimental groups and there was no impact of TrKB receptor inhibition. Combined, the results show that different early life stress schedules produce different behavioral and biological outcomes when measured at puberty. Combined with prior findings from more mature animals, the results presented here suggest that daily neonatal stress produces varied alterations in spatial cognition at different life stages with a transient learning deficit at puberty preceding a more persistent and a progressive memory impairment through adulthood and into aging.

6.
Hippocampus ; 30(5): 505-525, 2020 05.
Article in English | MEDLINE | ID: mdl-31626396

ABSTRACT

The neurobiology of postnatal hippocampal development in rodents is receiving increased attention as a means to address neurodevelopmental questions and to better understand the neural code(s) for spatial navigation in adulthood. We previously showed that spontaneous alternation (SA) in a Y-maze, which emerges at the end of the third postnatal week, was related to changes in fast glutamatergic synaptic transmission. In adults, oscillations in the hippocampal local field potential (LFP) (i.e., theta, 4-12 Hz; slow gamma, 25-55 Hz; and fast gamma, 65-100 Hz) have been shown to coordinate the activity of spatially tuned cell types in the hippocampus during route planning and execution. Other investigators have shown that theta activity matures during the first month of life. However, relationships between developmental alterations in gamma oscillations and cognitive function have not been investigated in juveniles, and the impact of developmental changes in excitatory synaptic transmission on network activity remains unclear. We implanted rats at postnatal day 14 to record LFPs from the synaptic layer of area CA1 during Y-maze exploration at postnatal Days 18, 19, 23, and 24. The positive allosteric modulator of AMPA receptors, CX614, or vehicle was administered prior to each test. We found that slow gamma peak frequency, but not peak power, remained constant across this age range. Fast gamma event rate increased with increasing age, while peak frequency decreased. AMPA receptor modulation impacted slow and fast gamma differently at different ages. Furthermore, gamma events showed relationships with novelty and movement speed that differed based on gamma sub-band (slow vs. fast). These results support the presence of environmentally-driven gamma oscillations in hippocampal network activity prior to the end of the third postnatal week of development. Differential refinement of slow and fast gamma occurring across the subsequent week supports involvement in the emergence of spatial navigation ability.


Subject(s)
Gamma Rhythm/physiology , Hippocampus/physiology , Locomotion/physiology , Maze Learning/physiology , Age Factors , Animals , Electrodes, Implanted , Female , Male , Rats , Rats, Long-Evans , Spatial Navigation/physiology
7.
Bio Protoc ; 8(22)2018 Nov 20.
Article in English | MEDLINE | ID: mdl-30560146

ABSTRACT

To better understand neural codes for spatial navigation and to address cognitive development questions, the neurobiology of postnatal hippocampal development is receiving increased attention. While the Morris Water Maze is the gold standard for assessing hippocampal integrity, potential confounds can be difficult to control for in juvenile rodents (around three weeks of age, when spatial navigation ability first emerges) and this wet maze is not amenable to electrophysiological recording. A dry maze alternative with minimal training, like the Barnes Maze adapted for juvenile rats, can help overcome these obstacles. This paper describes in detail the experimental procedure and data analyses for the adapted Barnes maze for juvenile animals.

8.
Learn Mem ; 25(6): 264-272, 2018 06.
Article in English | MEDLINE | ID: mdl-29764972

ABSTRACT

N-methyl-d-aspartate receptors (NMDARs) at excitatory synapses are central to activity-dependent synaptic plasticity and learning and memory. NMDARs act as ionotropic and metabotropic receptors by elevating postsynaptic calcium concentrations and by direct intracellular protein signaling. In the forebrain, these properties are controlled largely by the auxiliary GluN2 subunits, GluN2A and GluN2B. While calcium conductance through NMDAR channels and intracellular protein signaling make separate contributions to synaptic plasticity, it is not known if these properties individually influence learning and memory. To address this issue, we created chimeric GluN2 subunits containing the amino-terminal domain and transmembrane domains from GluN2A or GluN2B fused to the carboxy-terminal domain of GluN2B (termed ABc) or GluN2A ATD (termed BAc), respectively, and expressed these mutated GluN2 subunits in transgenic mice. Expression was confirmed at the mRNA level and protein subunit translation and translocation into dendrites were observed in forebrain neurons. In the spatial version of the Morris water maze, BAc mice displayed signs of a learning deficit. In contrast, ABc animals performed similarly to wild-types during training, but showed a more direct approach to the goal location during a long-term memory test. There was no effect of ABc or BAc expression in a nonspatial water escape task. Since background expression is predominantly GluN2A in mature animals, the results suggest that spatial learning is more sensitive to manipulations of the amino-terminal domain and transmembrane domains (calcium conductance) and long-term memory is regulated more by the carboxy-terminal domain (intracellular protein signaling).


Subject(s)
Maze Learning/physiology , Memory, Long-Term/physiology , Receptors, N-Methyl-D-Aspartate/metabolism , Amino Acid Sequence , Animals , Learning Disabilities/metabolism , Memory Disorders/metabolism , Mice, Transgenic , Neurons/metabolism , Prosencephalon/metabolism , Protein Domains , RNA, Messenger/metabolism , Receptors, N-Methyl-D-Aspartate/genetics , Spatial Behavior/physiology
9.
Learn Mem ; 25(3): 138-146, 2018 03.
Article in English | MEDLINE | ID: mdl-29449458

ABSTRACT

The neural bases of cognition may be greatly informed by relating temporally defined developmental changes in behavior with concurrent alterations in neural function. A robust improvement in performance in spatial learning and memory tasks occurs at 3 wk of age in rodents. We reported that the developmental increase of spontaneous alternation in a Y-maze was related to changes in temporal dynamics of fast glutamatergic synaptic transmission in the hippocampus. We also showed that, during allothetic behaviors in the Y-maze, network oscillation power increased at frequency bands known to support spatial learning and memory in adults. However, there are no discrete learning and memory phases during free exploration in the Y-maze. Thus, we adapted the Barnes maze for use with juvenile rats. Following a single platform exposure in dim light on the day before training (to encourage exploration), animals were trained on the subsequent 2 d in bright light to find a hidden escape box and then underwent a memory test 24 h later. During escape training, the older animals learned the task in 1 d, while the younger animals required 2 d and did not reach the performance of older animals. Long-term memory performance was also superior in the older animals. Thus, we have validated the use of the Barnes maze for this developmental period and established a timeline for the ontogeny of spatial navigation ability in this maze around 3 wk of age. Subsequent work will pair in vivo recording of hippocampal oscillations and single units with this task to help identify how hippocampal maturation might relate to performance improvements.


Subject(s)
Maze Learning , Neuropsychological Tests , Rats, Long-Evans/growth & development , Rats, Long-Evans/psychology , Spatial Navigation , Aging/psychology , Animals , Behavior, Animal , Female , Male , Spatial Memory
10.
Brain Res ; 1671: 1-13, 2017 Sep 15.
Article in English | MEDLINE | ID: mdl-28666957

ABSTRACT

Neural circuits in mammalian brains consist of large numbers of different cell types having different functional properties. To better understand the separate roles of individual neuron types in specific aspects of spatial learning and memory, we perturbed the function of principal neurons in vivo during maze performance or in hippocampal slices during recording of evoked excitatory synaptic potentials. Transgenic mice expressing the Drosophila allatostatin receptor (AlstR) in cortical and hippocampal pyramidal cells were tested on an elevated plus maze, in a Y-maze, and in the Morris water maze. Relative to a control cohort, AlstR-positive mice treated with allatostatin exhibited no difference in open arm dwell time on the elevated plus maze or total number of arm entries in a Y-maze, but displayed reduced spontaneous alternation. When animals received massed or spaced training trials in the Morris water maze, and the peptide was delivered prior to an immediate probe, no effects on performance were observed. When the peptide was delivered during a probe trial performed 24h after seven days of spaced training, allatostatin delivery to AlstR positive mice enhanced direct navigation to the escape platform. Combined, these results suggest that cortical and hippocampal pyramidal neurons are required during spatial decision-making in a novel environment and compete with other neural systems after extended training in a long-term reference memory task. In hippocampal slices collected from AlstR positive animals, allatostatin delivery produced frequency dependent alterations in the Schaffer collateral fiber volley (attenuated accommodation at 100Hz) and excitatory postsynaptic potential (attenuated facilitation at 5Hz). Combined, the neural and behavioral discoveries support the involvement of short-term plasticity of Schaffer collateral axons and synapses during exploration of a novel environment and during initial orientation to a goal in a well-learned setting.


Subject(s)
Drosophila Proteins/metabolism , Drosophila Proteins/physiology , Learning/physiology , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/physiology , Receptors, Neuropeptide/metabolism , Receptors, Neuropeptide/physiology , Spatial Memory/physiology , Animals , Axons/physiology , Drosophila/anatomy & histology , Drosophila/metabolism , Excitatory Postsynaptic Potentials , Hippocampus/metabolism , Hippocampus/physiology , Maze Learning/physiology , Memory/physiology , Memory, Long-Term/physiology , Mice , Mice, Transgenic , Neurons/physiology , Neuropeptides/metabolism , Neuropeptides/physiology , Prosencephalon/metabolism , Prosencephalon/physiology , Pyramidal Cells/physiology , Synaptic Transmission/physiology
11.
J Biomed Mater Res A ; 105(1): 159-168, 2017 01.
Article in English | MEDLINE | ID: mdl-27615364

ABSTRACT

Intracortical probe technology, consisting of arrays of microelectrodes, offers a means of recording the bioelectrical activity from neural tissue. A major limitation of existing intracortical probe technology pertains to limited lifetime of 6 months to a year of recording after implantation. A major contributor to device failure is widely believed to be the interfacial mechanical mismatch of conventional stiff intracortical devices and the surrounding brain tissue. We describe the design, development, and demonstration of a novel functional intracortical probe technology that has a tunable Young's modulus from ∼2 GPa to ∼50 MPa. This technology leverages advances in dynamically softening materials, specifically thiol-ene/acrylate thermoset polymers, which exhibit minimal swelling of < 3% weight upon softening in vitro. We demonstrate that a shape memory polymer-based multichannel intracortical probe can be fabricated, that the mechanical properties are stable for at least 2 months and that the device is capable of single unit recordings for durations up to 77 days in vivo. This novel technology, which is amenable to processes suitable for manufacturing via standard semiconductor fabrication techniques, offers the capability of softening in vivo to reduce the tissue-device modulus mismatch to ultimately improve long term viability of neural recordings. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 159-168, 2017.


Subject(s)
Brain Waves , Frontal Lobe/physiology , Animals , Elastic Modulus , Electrodes , Mice
13.
Front Neurosci ; 10: 301, 2016.
Article in English | MEDLINE | ID: mdl-27445672

ABSTRACT

Implantable microelectrode arrays (MEAs) offer clinical promise for prosthetic devices by enabling restoration of communication and control of artificial limbs. While proof-of-concept recordings from MEAs have been promising, work in animal models demonstrates that the obtained signals degrade over time. Both material robustness and tissue response are acknowledged to have a role in device lifetime. Amorphous Silicon carbide (a-SiC), a robust material that is corrosion resistant, has emerged as an alternative encapsulation layer for implantable devices. We systematically examined the impact of a-SiC coating on Si probes by immunohistochemical characterization of key markers implicated in tissue-device response. After implantation, we performed device capture immunohistochemical labeling of neurons, astrocytes, and activated microglia/macrophages after 4 and 8 weeks of implantation. Neuron loss and microglia activation were similar between Si and a-SiC coated probes, while tissue implanted with a-SiC displayed a reduction in astrocytes adjacent to the probe. These results suggest that a-SiC has a similar biocompatibility profile as Si, and may be suitable for implantable MEA applications as a hermetic coating to prevent material degradation.

14.
Acta Biomater ; 32: 57-67, 2016 Mar 01.
Article in English | MEDLINE | ID: mdl-26689462

ABSTRACT

Microelectrode arrays have been extensively utilized to record extracellular neuronal activity for brain-machine interface applications. Modifying the microelectrodes with conductive polymers such as poly(3,4-ethylenedioxythiophene) (PEDOT) has been reported to be advantageous because it increases the effective surface area of the microelectrodes, thereby decreasing impedance and enhancing charge transfer capacity. However, the long term stability and integrity of such coatings for chronic recordings remains unclear. Previously, our group has demonstrated that use of the smaller counter ion tetrafluoroborate (TFB) during electrodeposition increased the stability of the PEDOT coatings in vitro compared to the commonly used counter ion poly(styrenesulfonate) (PSS). In the current work, we examined the long-term in vivo performance of PEDOT-TFB coated microelectrodes. To do so, we selectively modified half of the microelectrodes on NeuroNexus single shank probes with PEDOT-TFB while the other half of the microelectrodes were modified with gold as a control. The modified probes were then implanted into the primary motor cortex of rats. Single unit recordings were observed on both PEDOT-TFB and gold control microelectrodes for more than 12 weeks. Compared to the gold-coated microelectrodes, the PEDOT-TFB coated microelectrodes exhibited an overall significantly lower impedance and higher number of units per microelectrode specifically for the first four weeks. The majority of PEDOT-TFB microelectrodes with activity had an impedance magnitude lower than 400 kΩ at 1 kHz. Our equivalent circuit modeling of the impedance data suggests stability in the polymer-related parameters for the duration of the study. In addition, when comparing PEDOT-TFB microelectrodes with and without long-term activity, we observed a distinction in certain circuit parameters for these microelectrodes derived from equivalent circuit modeling prior to implantation. This observation may prove useful in qualifying PEDOT-TFB microelectrodes with a greater likelihood of registering long-term activity. Overall, our findings confirm that PEDOT-TFB is a chronically stable coating for microelectrodes to enable neural recording. STATEMENT OF SIGNIFICANCE: Microelectrode arrays have been extensively utilized to record extracellular neuronal activity for brain-machine interface applications. Poly(3,4-ethylenedioxythiophene) (PEDOT) has gained interest because of its unique electrochemical characteristics and its excellent intrinsic electrical conductivity. However, the long-term stability of the PEDOT film, especially for chronic neural applications, is unclear. In this manuscript, we report for the first time the use of highly stable PEDOT doped with tetrafluoroborate (TFB) for long-term neural recordings. We show that PEDOT-TFB coated microelectrodes on average register more units compared to control gold microelectrodes for at least first four weeks post implantation. We collected the in vivo impedance data over a wide frequency spectrum and developed an equivalent circuit model which helped us determine certain parameters to distinguish between PEDOT-TFB microelectrodes with and without long-term activity. Our findings suggest that PEDOT-TFB is a chronically stable coating for neural recording microelectrodes. As such, PEDOT-TFB could facilitate chronic recordings with ultra-small and high-density neural arrays.


Subject(s)
Boric Acids/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Cerebral Cortex/cytology , Coated Materials, Biocompatible/pharmacology , Neurons/physiology , Polymers/pharmacology , Animals , Borates , Dielectric Spectroscopy , Electric Impedance , Electrodes, Implanted , Female , Gold , Microelectrodes , Neurons/drug effects , Rats, Long-Evans
15.
Brain Res ; 1629: 1-9, 2015 Dec 10.
Article in English | MEDLINE | ID: mdl-26453830

ABSTRACT

In vitro assays offer a means of screening potential therapeutics and accelerating the drug development process. Here, we utilized neuronal cultures on planar microelectrode arrays (MEA) as a functional assay to assess the neurotoxicity of amyloid-ß 1-42 (Aß42), a biomolecule implicated in the Alzheimer׳s disease (AD). In this approach, neurons harvested from embryonic mice were seeded on the substrate-integrated microelectrode arrays. The cultured neurons form a spontaneously active network, and the spiking activity as a functional endpoint could be detected via the MEA. Aß42 oligomer, but not monomer, significantly reduced network spike rate. In addition, we demonstrated that the ionotropic glutamate receptors, NMDA and AMPA/kainate, play a role in the effects of Aß42 on neuronal activity in vitro. To examine the utility of the MEA-based assay for AD drug discovery, we tested two model therapeutics for AD, methylene blue (MB) and memantine. Our results show an almost full recovery in the activity within 24h after administration of Aß42 in the cultures pre-treated with either MB or memantine. Our findings suggest that cultured neuronal networks may be a useful platform in screening potential therapeutics for Aß induced changes in neurological function.


Subject(s)
Amyloid beta-Peptides/toxicity , Nerve Net/drug effects , Nerve Net/physiology , Neurons/drug effects , Neurons/physiology , Peptide Fragments/toxicity , Action Potentials/drug effects , Action Potentials/physiology , Alzheimer Disease/drug therapy , Animals , Cells, Cultured , Drug Evaluation, Preclinical/methods , Female , Memantine/pharmacology , Memantine/therapeutic use , Mice , Pregnancy , Receptors, N-Methyl-D-Aspartate/agonists , Receptors, N-Methyl-D-Aspartate/physiology
16.
Dev Cogn Neurosci ; 12: 145-54, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25752732

ABSTRACT

Metaplasticity refers to adjustment in the requirements for induction of synaptic plasticity based on the prior history of activity. Numerous forms of developmental metaplasticity are observed at Schaffer collateral synapses in the rat hippocampus at the end of the third postnatal week. Emergence of spatial learning and memory at this developmental stage suggests possible involvement of metaplasticity in the final maturation of the hippocampus. Three distinct metaplastic phenomena are apparent. (1) As transmitter release probability increases with increasing age, presynaptic potentiation is reduced. (2) Alterations in the composition and channel conductance properties of AMPARs facilitate the induction of postsynaptic potentiation with increasing age. (3) Low frequency stimulation inhibits subsequent induction of potentiation in animals older but not younger than 3 weeks of age. Thus, many forms of plasticity expressed at SC-CA1 synapses are different in rats younger and older than 3 weeks of age, illustrating the complex orchestration of physiological modifications that underlie the maturation of hippocampal excitatory synaptic transmission. This review paper describes three late postnatal modifications to synaptic plasticity induction in the hippocampus and attempts to relate these metaplastic changes to developmental alterations in hippocampal network activity and the maturation of contextual learning.


Subject(s)
Aging/physiology , Hippocampus/physiology , Learning/physiology , Neuronal Plasticity/physiology , Synapses/physiology , Animals , Long-Term Potentiation , Long-Term Synaptic Depression , Rats
17.
Neurosci Biobehav Rev ; 43: 183-90, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24769291

ABSTRACT

The hippocampus is not fully developed at birth and, with respect to spatial cognition, only begins to show signs of adult-like function at three postnatal weeks in rodents. Studying the developmental period spanning roughly two to four weeks of age permits an understanding of the neural framework necessary for the emergence of spatial navigation and, quite possibly, human episodic memory. However, due to developmental factors, behavior data collection and interpretation can be severely compromised if inappropriate designs are applied. As such, we propose methodological considerations for the behavioral assessment of hippocampal function in developing rats that take into account animal size, growth rate, and sensory and motor ability. We further summarize recent key interdisciplinary studies that are beginning to unravel the molecular machinery and physiological alterations responsible for hippocampal maturation. In general, hippocampal development is a protracted process during which unique contributions to spatial cognition and complex recognition memory come "on line" at different postnatal ages creating a unique situation for elucidating the neural bases of specific components of higher cognitive abilities.


Subject(s)
Cognition/physiology , Hippocampus/physiology , Memory, Episodic , Recognition, Psychology/physiology , Spatial Behavior/physiology , Animals , Humans , Interdisciplinary Studies
18.
Acta Biomater ; 10(6): 2446-54, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24576579

ABSTRACT

Conducting polymers, especially poly(3,4-ethylenedioxythiophene) (PEDOT) based materials, are important for developing highly sensitive and microscale neural probes. In the present work, we show that the conductivity and stability of PEDOT can be significantly increased by switching the widely used counter anion poly(styrenesulfonate) (PSS) to the smaller tetrafluoroborate (TFB) anion during the electrodeposition of the polymer. Time-dependent impedance measurements of polymer modified implantable microwires were conducted in physiological buffer solutions under accelerated aging conditions and the relative stability of PEDOT:PSS and PEDOT:TFB modified microwires was compared over time. This study was also extended to carbon nanotube (CNT) incorporated PEDOT:PSS which, according to some reports, is claimed to enhance the stability and electrical performance of the polymer. However, no noticeable difference was observed between PEDOT:PSS and CNT:PEDOT:PSS in our measurements. At the biologically relevant frequency of 1kHz, PEDOT:TFB modified microwires exhibit approximately one order of magnitude higher conductivity and demonstrate enhanced stability over both PEDOT:PSS and CNT:PEDOT:PSS modified microwires. In addition, PEDOT:TFB is not neurotoxic and we show the proof-of-concept for both in vitro and in vivo neuronal recordings using PEDOT:TFB modified microelectrode arrays and chronic electrodes, respectively. Our findings suggest that PEDOT:TFB is a promising conductive polymer coating for the recording of neural activities.


Subject(s)
Brain-Computer Interfaces , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Polymers/chemistry , Microscopy, Electron, Scanning
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