scholarly journals Uncoupling PSD-95 Interactions Leads to Rapid Recovery of Cortical Function after Focal Stroke

2013 ◽  
Vol 33 (12) ◽  
pp. 1937-1943 ◽  
Author(s):  
Luka R Srejic ◽  
William D Hutchison ◽  
Michelle M Aarts

Since the most significant ischemic sequelae occur within hours of stroke, it is necessary to understand how neuronal function changes during this time. While histologic and behavioral models show the extent of stroke-related damage, only in vivo recordings can illustrate changes in brain activity during stroke and validate effectiveness of neuroprotective compounds. Spontaneous and evoked field potentials (fEPs) were recorded in the deep layers of the cortex with a linear microelectrode array for 3 hours after focal stroke in anesthetized rats. Tat-NR2B9c peptide, which confers neuroprotection by uncoupling the PSD-95 protein from N-methyl-D-aspartate receptor (NMDAR), was administered 5 minutes before ischemia. Evoked field potentials were completely suppressed within 3 minutes of infarct in all ischemic groups. Evoked field potential recovery after stroke in rats treated with Tat-NR2B9c (83% of baseline) was greater compared with stroke-only (61% of baseline) or control peptide (Tat-NR2B-AA; 67% of baseline) groups ( P<0.001). Electroencephalography (EEG) power was higher in Tat-NR2B9c-treated animals at both 20 minutes and 1 hour (50% and 73% of baseline, respectively) compared with stroke-only and Tat-NR2B-AA-treated rats ( P<0.05). Tat-NR2B9c significantly reduces stroke-related cortical dysfunction as evidenced by greater recovery of fEPs and EEG power; illustrating the immediate effects of the compound on poststroke brain function.

2004 ◽  
Vol 92 (2) ◽  
pp. 1226-1235 ◽  
Author(s):  
Douglas A. Caruana ◽  
C. Andrew Chapman

Although a major output of the hippocampal formation is from the subiculum to the deep layers of the entorhinal cortex, the parasubiculum projects to the superficial layers of the entorhinal cortex and may therefore modulate how the entorhinal cortex responds to sensory inputs from other cortical regions. Recordings at multiple depths in the entorhinal cortex were first used to characterize field potentials evoked by stimulation of the parasubiculum in urethan-anesthetized rats. Current source density analysis showed that a prominent surface-negative field potential component is generated by synaptic activation in layer II. The surface-negative field potential was also observed in rats with chronically implanted electrodes. The response was maintained during short stimulation trains of ≤125 Hz, suggesting that it is generated by activation of monosynaptic inputs to the entorhinal cortex. The piriform cortex also projects to layer II of the entorhinal cortex, and interactions between parasubicular and piriform cortex inputs were investigated using double-site stimulation tests. Simultaneous activation of parasubicular and piriform cortex inputs with high-intensity pulses resulted in smaller synaptic potentials than were expected on the basis of summing the individual responses, consistent with the termination of both pathways onto a common population of neurons. Paired-pulse tests were then used to assess the effect of parasubicular stimulation on responses to piriform cortex stimulation. Responses of the entorhinal cortex to piriform cortex inputs were inhibited when the parasubiculum was stimulated 5 ms earlier and were enhanced when the parasubiculum was stimulated 20–150 ms earlier. These results indicate that excitatory inputs to the entorhinal cortex from the parasubiculum may enhance the propagation of neuronal activation patterns into the hippocampal circuit by increasing the responsiveness of the entorhinal cortex to appropriately timed inputs.


2013 ◽  
Vol 109 (4) ◽  
pp. 940-947 ◽  
Author(s):  
Matthew A. Smith ◽  
Xiaoxuan Jia ◽  
Amin Zandvakili ◽  
Adam Kohn

Neuronal responses are correlated on a range of timescales. Correlations can affect population coding and may play an important role in cortical function. Correlations are known to depend on stimulus drive, behavioral context, and experience, but the mechanisms that determine their properties are poorly understood. Here we make use of the laminar organization of cortex, with its variations in sources of input, local circuit architecture, and neuronal properties, to test whether networks engaged in similar functions but with distinct properties generate different patterns of correlation. We find that slow timescale correlations are prominent in the superficial and deep layers of primary visual cortex (V1) of macaque monkeys, but near zero in the middle layers. Brief timescale correlation (synchrony), on the other hand, was slightly stronger in the middle layers of V1, although evident at most cortical depths. Laminar variations were also apparent in the power of the local field potential, with a complementary pattern for low frequency (<10 Hz) and gamma (30–50 Hz) power. Recordings in area V2 revealed a laminar dependence similar to V1 for synchrony, but slow timescale correlations were not different between the input layers and nearby locations. Our results reveal that cortical circuits in different laminae can generate remarkably different patterns of correlations, despite being tightly interconnected.


1996 ◽  
Vol 13 (4) ◽  
pp. 747-758 ◽  
Author(s):  
J. C. Dye ◽  
H. J. Karten

AbstractWe have developed two brain slice preparations for studying tectofugal visual pathways in the chick: conventional, 400-μm slices (“thin slices”), and “thick slices” which encompass the rostral pole of the optic tectum and the contralateral optic nerve. Stimulation was delivered with a bipolar electrode positioned in stratum opticum in thin slices and in the contralateral optic nerve in thick slices. While the latter preparation provided a means of exclusively and unambiguously activating retinal afferents, several lines of evidence also indicated that the evoked field potentials in thin slices were chiefly consequent to retinal afferent excitation: (1) the similarity of evoked field potentials in thin slices to those in thick slice preparations; (2) their precise localization in retinorecipient layers as shown by prelabeling from retina with FITC-coupled cholera toxin; (3) transmission delays appropriate for retinal afferents as established with the thick slice preparation; (4) patterns of labeled afferents resulting from applications of Dil crystals to slices fixed after recording; and (5) the similarity in transmitter pharmacology between thin and thick slice preparations. Pharmacological manipulations carried out with bath-applied antagonists indicated that glutamate is the principal retinotectal transmitter. The broadly active glutamate receptor blocker, kynurenic acid, reversibly eliminated the postsynaptic component of the field potential as confirmed with 0 Ca2+ saline. A complete block was also effected by the non-NMDA antagonists CNQX and DNQX. The specific NMDA antagonist, APS, caused a smaller and variable reduction in response amplitude. The GABA antagonist, bicuculline, caused a prolongation of the monosynaptic field epsp in retinorecipient layers and an enhancement of the long-latency, negative wave in cellular layers below, supporting a late, excitation-limiting role for this inhibitory transmitter.


2017 ◽  
Author(s):  
Ana Parabucki ◽  
Ilan Lampl

SummaryLocal field potentials are an important measure of brain activity and have been used to address various mechanistic and behavioral questions. We revealed a prominent whisker evoked local field potential signal in the olfactory bulb and investigated its physiology. This signal, dependent on barrel cortex activation and highly correlated with its local activity, represented a pure volume conductance signal that was sourced back to the activity in the ventro-lateral orbitofrontal cortex, located a few millimeters away. Thus, we suggest that special care should be taken when acquiring and interpreting LFP data.


2017 ◽  
Author(s):  
Shigenori Inagaki ◽  
Masakazu Agetsuma ◽  
Shinya Ohara ◽  
Toshio Iijima ◽  
Tetsuichi Wazawa ◽  
...  

AbstractElectrophysiological field potential dynamics have been widely used to investigate brain functions and related psychiatric disorders. Conversely, however, various technical limitations of conventional recording methods have limited its applicability to freely moving subjects, especially when they are in a group and socially interacting with each other. Here, we propose a new method to overcome these technical limitations by introducing a bioluminescent voltage indicator called LOTUS-V. Using our simple and fiber-free recording method, named “SNIPA,” we succeeded in capturing brain activity in freely-locomotive mice, without the need for complicated instruments. This novel method further allowed us to simultaneously record from multiple independently-locomotive animals that were interacting with one another. Further, we successfully demonstrated that the primary visual cortex was activated during the interaction. This methodology will further facilitate a wide range of studies in neurobiology and psychiatry.


2018 ◽  
Vol 120 (5) ◽  
pp. 2232-2245 ◽  
Author(s):  
Nicholas J. Michelson ◽  
Takashi D. Y. Kozai

General anesthesia is ubiquitous in research and medicine, yet although the molecular mechanisms of anesthetics are well characterized, their ultimate influence on cortical electrophysiology remains unclear. Moreover, the influence that different anesthetics have on sensory cortexes at neuronal and ensemble scales is mostly unknown and represents an important gap in knowledge that has widespread relevance for neural sciences. To address this knowledge gap, this work explored the effects of isoflurane and ketamine/xylazine, two widely used anesthetic paradigms, on electrophysiological behavior in mouse primary visual cortex. First, multiunit activity and local field potentials were examined to understand how each anesthetic influences spontaneous activity. Then, the interlaminar relationships between populations of neurons at different cortical depths were studied to assess whether anesthetics influenced resting-state functional connectivity. Lastly, the spatiotemporal dynamics of visually evoked multiunit and local field potentials were examined to determine how each anesthetic alters communication of visual information. We found that isoflurane enhanced the rhythmicity of spontaneous ensemble activity at 10–40 Hz, which coincided with large increases in coherence between layer IV with superficial and deep layers. Ketamine preferentially increased local field potential power from 2 to 4 Hz, and the largest increases in coherence were observed between superficial and deep layers. Visually evoked responses across layers were diminished under isoflurane, and enhanced under ketamine anesthesia. These findings demonstrate that isoflurane and ketamine anesthesia differentially impact sensory processing in V1. NEW & NOTEWORTHY We directly compared electrophysiological responses in awake and anesthetized (isoflurane or ketamine) mice. We also proposed a method for quantifying and visualizing highly variable, evoked multiunit activity. Lastly, we observed distinct oscillatory responses to stimulus onset and offset in awake and isoflurane-anesthetized mice.


2007 ◽  
Vol 98 (3) ◽  
pp. 1697-1705 ◽  
Author(s):  
Fredrik Bengtsson ◽  
Henrik Jörntell

The last few years have seen an increase in the variety of in vivo experiments used for studying cerebellar physiological mechanisms. A combination of ketamine and xylazine has become a particularly popular form of anesthesia. However, because nonanesthetized control conditions are lacking in these experiments, so far there has been no evaluation of the effects of these drugs on the physiological activity in the cerebellar neuronal network. In the present study, we used the mossy fiber, parallel fiber, and climbing fiber field potentials evoked in the nonanesthetized, decerebrated rat to serve as a control condition against which the effects of intravenous drug injections could be compared. All anesthetics were applied at doses required for normal maintenance of anesthesia. We found that ketamine substantially depressed the evoked N3 field potential, which is an indicator of the activity in the parallel fiber synapses (−40%), and nearly completely abolished evoked climbing fiber field potentials (−90%). Xylazine severely depressed the N3 field (−75%) and completely abolished the climbing fiber field (−100%). In a combination commonly used for general anesthesia (20:1), ketamine–xylazine injections also severely depressed the N3 field (−75%) and nearly completely abolished the climbing fiber field (−90%). We also observed that lowered body and surface temperatures (<34°C) resulted in a substantial depression of the N3 field (−50%). These results urge for some caution in the interpretations of studies on cerebellar network physiology performed in animals anesthetized with these drugs.


1993 ◽  
Vol 69 (4) ◽  
pp. 1276-1291 ◽  
Author(s):  
D. A. Prince ◽  
G. F. Tseng

1. Field potentials and intracellular activities were examined in neocortical slices obtained through areas of chronic cortical injury produced by cortical undercutting and transcortical lesions made in vivo 7-122 days before the terminal in vitro slice experiment. 2. Abnormal field potentials characterized by long- and variable-latency multiphasic events could be evoked by layer VI-white matter or subpial stimulation in 9 of 15 animals that had adequate partial cortical isolations. These "epileptiform" field potentials were recorded in layers II-V and propagated across the cortex. They appeared at threshold in an all-or-none fashion and, in most slices, could be blocked by increasing stimulus intensity. In one slice, spontaneous epileptiform events occurred that were similar to those evoked by extracellular stimulation. 3. Intracellular activities during the epileptiform field potentials consisted of polyphasic synaptic events that were predominantly depolarizing and that could last < or = 400-500 ms, synchronous with the field potential activities. A variety of observations suggested that the neuronal activities underlying epileptiform field potentials were relatively asynchronous and much less intense than those previously found in chemically induced epileptogenesis within the neocortex. 4. Inhibitory postsynaptic potentials (IPSPs) were not prominent in neurons when threshold stimuli evoked epileptiform events; however, suprathreshold stimuli could elicit biphasic IPSPs and block the long-latency polysynaptic activity and abnormal field potential in most slices. Depolarizing components of the polysynaptic activity had the appearance of excitatory postsynaptic potentials in terms of their responses to alterations in membrane potential. 5. Comparison of spike parameters in layer V neurons of epileptogenic slices with those in control layer V neurons showed no significant differences in spike height, threshold, duration, or rise time. Resting membrane potentials were also not significantly different. 6. There was a highly significant difference in input resistance (RN) between layer V neurons in control and injured slices; the mean value for neurons in lesioned cortex was 68.1 M omega, whereas that in control cells was 30.5 M omega. There was also a significant prolongation of the slow membrane time constant in neurons of injured cortex (19.4 ms) as opposed to that in control cells (12.2 ms), suggesting that a change in specific resistivity or capacitance contributed to the higher RNS. 7. The relationship between adapted spike frequency and applied current (f-I slope) was steeper in layer V neurons from injured cortical slices (44.3 Hz/nA) than in normal layer V cells (28.2 Hz/nA).(ABSTRACT TRUNCATED AT 400 WORDS)


2018 ◽  
Author(s):  
Alexandra P. Chatzikalymniou ◽  
Frances K. Skinner

AbstractOscillations in local field potentials (LFPs) commonly occur and analyses of them fuel brain function hypotheses. An understanding of the cellular correlates and pathways affecting LFPs is needed but many overlapping pathways in vivo makes this difficult to achieve. A prevalent LFP rhythm in the hippocampus is ‘theta’ (3-12 Hz). Theta rhythms emerge intrinsically in an in vitro whole hippocampus preparation and thus can be produced by local interactions between interneurons and pyramidal (PYR) cells. Overlapping pathways are much reduced in this preparation making it possible to decipher the contribution of different cell types to LFP generation. We focus on oriens-lacunosum/moleculare (OLM) cells as a major class of interneurons in the hippocampus. They can influence PYR cells through two distinct pathways, (i) by direct inhibition of PYR cell distal dendrites, and (ii) by indirect disinhibition of PYR cell proximal dendrites by inhibiting bistratified cells (BiCs) that target them. We use previous inhibitory network models and build biophysical LFP models using volume conductor theory. We assess the effect of OLM cells to ongoing intrinsic LFP theta rhythms by directly comparing our model LFP features with experiment. We find that robust LFP theta responses adhering to reproducible experimental criteria occur only for particular connectivities between OLM cells and BiCs. Decomposition of the LFP reveals that OLM cell inputs onto the PYR cell regulate robustness of LFP responses without affecting average power and that the robust response depends on co-activation of distal inhibition and basal excitation. We use our models to estimate the spatial extent of the region generating LFP theta rhythms, leading us to predict that about 22,000 PYR cells participate in generating the LFP theta rhythm. Besides allowing us to understand OLM cells’ contributions to intrinsic theta rhythms, our work can drive hypothesis developments of cellular contributions in vivo.Author SummaryOscillatory local field potentials (LFPs) are extracellularly recorded potentials that are widely used to interpret information processing in the brain. For example, theta LFP rhythms (3-12 Hz) are correlated with memory processing and it is known that particular inhibitory cell types control their existence. As such, it is critical for us to appreciate how various cell types contribute to the characteristics of LFP rhythms. A precise biophysical modeling scheme linking activity at the cellular level and the recorded signal has been established. However, it is difficult to assess cellular contributions in vivo because of many spatiotemporally overlapping pathways that prevent the unambiguous separation of signals. Using an in vitro preparation that exhibits intrinsic theta (3-12 Hz) rhythms and where there is much less overlap, we build biophysical LFP models to explore cell contributions to ongoing intrinsic theta rhythms. We uncover distinct contributions from different cell types and show that robust theta rhythms depend specifically on one of the cell types. We are able to determine this because our LFP models have direct links with experiment and we are able to perform thousands of simulations.


2021 ◽  
Vol 12 ◽  
Author(s):  
Miranda J. Francoeur ◽  
Tianzhi Tang ◽  
Leila Fakhraei ◽  
Xuanyu Wu ◽  
Sidharth Hulyalkar ◽  
...  

Rodent models of cognitive behavior have greatly contributed to our understanding of human neuropsychiatric disorders. However, to elucidate the neurobiological underpinnings of such disorders or impairments, animal models are more useful when paired with methods for measuring brain function in awake, behaving animals. Standard tools used for systems-neuroscience level investigations are not optimized for large-scale and high-throughput behavioral battery testing due to various factors including cost, time, poor longevity, and selective targeting limited to measuring only a few brain regions at a time. Here we describe two different “user-friendly” methods for building extracellular electrophysiological probes that can be used to measure either single units or local field potentials in rats performing cognitive tasks. Both probe designs leverage several readily available, yet affordable, commercial products to facilitate ease of production and offer maximum flexibility in terms of brain-target locations that can be scalable (32–64 channels) based on experimental needs. Our approach allows neural activity to be recorded simultaneously with behavior and compared between micro (single unit) and more macro (local field potentials) levels of brain activity in order to gain a better understanding of how local brain regions and their connected networks support cognitive functions in rats. We believe our novel probe designs make collecting electrophysiology data easier and will begin to fill the gap in knowledge between basic and clinical research.


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