Howard Gritton - Academia.edu (original) (raw)

Papers by Howard Gritton

The Journal of Neuroscience, Sep 26, 2012

Nature Precedings, Oct 14, 2011

REM sleep enhances hippocampus-dependent associative memory but has little impact on striatal-dep... more REM sleep enhances hippocampus-dependent associative memory but has little impact on striatal-dependent procedural learning 1-3. Antidepressant medications like desipramine (DMI) inhibit rapid-eye-movement (REM) sleep but it is little understood how antidepressant treatments affect learning. We found that DMI strongly suppressed REM sleep in rats for several hours and impaired reconsolidation of a familiar maze and consolidation of moved baited positions (reversal learning) in a sleep-dependent fashion. Unexpectedly, DMI also reduced the spindle-rich transitionto-REM sleep state (TR) and spatial memory changes were more related to TR than to REM sleep. Working memory was unaffected, but overnight reference memory was significantly impaired and subjects increased reliance on non-hippocampal strategies. Procedural memory performance was positively correlated with increases in non-REM sleep after DMI serving to offset memory declines, partially preserving performance. Our results suggest that familiar memories are reconsolidated during REM sleep, reversal memories consolidated during TR, and procedural memories consolidated during non-REM sleep.

Scientific reports, Jan 8, 2016

Advances in neurotechnology have been integral to the investigation of neural circuit function in... more Advances in neurotechnology have been integral to the investigation of neural circuit function in systems neuroscience. Recent improvements in high performance fluorescent sensors and scientific CMOS cameras enables optical imaging of neural networks at a much larger scale. While exciting technical advances demonstrate the potential of this technique, further improvement in data acquisition and analysis, especially those that allow effective processing of increasingly larger datasets, would greatly promote the application of optical imaging in systems neuroscience. Here we demonstrate the ability of wide-field imaging to capture the concurrent dynamic activity from hundreds to thousands of neurons over millimeters of brain tissue in behaving mice. This system allows the visualization of morphological details at a higher spatial resolution than has been previously achieved using similar functional imaging modalities. To analyze the expansive data sets, we developed software to facili...

Nature, 2004

some similarity values were equal to zero (that is, no OTUs in common), we coded the similarity d... more some similarity values were equal to zero (that is, no OTUs in common), we coded the similarity data by adding 0.01 before log transforming each value 29. The approach outlined in ref. 14 allowed us to use relative comparisons of bacterial community composition rather than richness to examine the taxa-area relationship; richness is very difficult to estimate accurately in hyperdiverse communities such as bacterial communities. There is no reason to believe that undersampling and/or PCR biases will co-vary with intersample distance or will result in preferential sampling of those taxa most likely to be shared among samples located close together in space; thus, these factors, although likely to be present, are unlikely to influence the z-values we observed. In addition, we can think of no model in which PCR biases and/or undersampling could generate a taxa-area relationship that was completely artefactual. We compared the z-values for different taxon definitions by testing if the slopes of the regressions differed (see Supplementary Methods 2). We used the same distance decay approach to determine the z-value for plants, using data from the transect quadrants. Influence of habitat heterogeneity We used partial Mantel tests (9,999 permutations) to examine the influence of abiotic factors and aboveground plant composition on bacterial community composition, while holding geographic distance constant and vice versa. We constructed a distance matrix for plant community composition from per cent cover estimates for the four dominant species (Spartina alterniflora, Spartina patens, Salicornia virginica and Limonium nashii). We constructed a matrix of environmental distance from the abiotic factors identified as most important to community composition (phosphate and ammonia concentrations), using BIO-ENV 28. The BIO-ENV procedure selects a subset of available abiotic variables to maximize rank correlation between community similarity and abiotic dissimilarity matrices. We then used these matrices to test for additional distance and plant effects.

Neurobiology of learning and memory, Jan 18, 2016

In addition to the neuromodulatory role of cholinergic systems, brief, temporally discrete cholin... more In addition to the neuromodulatory role of cholinergic systems, brief, temporally discrete cholinergic release events, or "transients", have been associated with the detection of cues in attention tasks. Here we review four main findings about cholinergic transients during cognitive processing. Cholinergic transients are: (1) associated with the detection of a cue and influenced by cognitive state; (2) not dependent on reward outcome, although the timing of the transient peak co-varies with the temporal relationship between detection and reward delivery; (3) correlated with the mobilization of the cue-evoked response; (4) causal mediators of shifts from monitoring to cue detection. We next discuss some of the key questions concerning the timing and occurrence of transients within the framework of available evidence including: (1) Why does the shift from monitoring to cue detection require a transient? (2) What determines whether a cholinergic transient will be generated? (...

In loving memory of Howard Earl Gritton My father passed far too early but I feel his presence ev... more In loving memory of Howard Earl Gritton My father passed far too early but I feel his presence everyday of my life and I thank him for his guidance, wisdom, and love. iii Acknowledgements My time at Michigan has been filled with both struggle and success. I have made new friends, grown older and hopefully wiser, gotten married, and had my first child. I will always look back on this time in my life with a great deal of fondness and appreciation. Since my first days of graduate school, I have received a great deal of support, help, and encouragement from the University, from the outstanding faculty, and countless undergraduates, graduate students, post-doc's and support staff. The research presented in this dissertation is a collection of the efforts of many beyond my own and they deserve my sincere thanks and praise. In particular I would like to thank the Lee lab members

We present a single-shot multiplane widefield imaging strategy using a z-splitter prism, which ca... more We present a single-shot multiplane widefield imaging strategy using a z-splitter prism, which can be assembled from off-the-self components and only requires a single camera. We further introduce a novel extended-volume 3D deconvolution strategy to suppress far-out-of-focus fluorescence background to significantly improve the contrast of our recorded images, conferring to our system a capacity for quasi optical sectioning. By swapping in different z-splitter configurations, we can prioritize high speed or large 3D field-of-view imaging depending on the application of interest. Moreover, our system can be readily applied to a variety of imaging modalities in addition to fluorescence, such as phase-contrast and darkfield imaging, making it a versatile tool for a wide range of biological or biomedical imaging applications.

Biomedical Optics Express

The inherent constraints on resolution, speed and field of view have hindered the development of ... more The inherent constraints on resolution, speed and field of view have hindered the development of high-speed, three-dimensional microscopy techniques over large scales. Here, we present a multiplane line-scan imaging strategy, which uses a series of axially distributed reflecting slits to probe different depths within a sample volume. Our technique enables the simultaneous imaging of an optically sectioned image stack with a single camera at frame rates of hundreds of hertz, without the need for axial scanning. We demonstrate the applicability of our system to monitor fast dynamics in biological samples by performing calcium imaging of neuronal activity in mouse brains and voltage imaging of cardiomyocytes in cardiac samples.

Fast, volumetric imaging over large scales has been a long-standing challenge in biological micro... more Fast, volumetric imaging over large scales has been a long-standing challenge in biological microscopy. To address this issue, we developed a variant of confocal microscopy that provides simultaneous multiplane imaging over large field of view and at video rate. Our apparatus, called multi-Z confocal microscopy, differs from a conventional confocal microscope in both its illumination and detection parts. First, axially elongated illumination is achieved by under filling the back aperture of the microscope objective. The resulting low NA provides an axial extent of the illumination of the order of 100 µm. The light from the sample is then collected by the same objective, now taking advantage of the full NA which ensures high collection efficiency, and send to the detection unit. The latter is comprised by four reflecting pinholes axially distributed in the image plane such that they are conjugated to different depths within the sample. Each detection channel spans a probe volume at a...

Recent improvements in genetically encoded voltage indicators enabled optical imaging of action p... more Recent improvements in genetically encoded voltage indicators enabled optical imaging of action potentials and subthreshold membrane voltage dynamics from single neurons in the mammalian brain. To perform high speed voltage imaging, widefield microscopy remains an essential tool for recording activity from many neurons simultaneously over a large anatomical area. However, the lack of optical sectioning makes widefield microscopy more prone to background signal contamination, and thus far voltage imaging using fully genetically encoded voltage indicators remains limited to simultaneous sampling of a few cells over a restricted field-of-view. We here demonstrate a strategy for large scale voltage imaging using the fully genetically encoded voltage indicator SomArchon and targeted illumination. We implemented a simple, low-cost digital micromirror device based targeted illumination strategy to restrict illumination to the cells of interest, and systematically quantified the improvement...

Cortical synchrony is theorized to contribute to communication between connected networks during ... more Cortical synchrony is theorized to contribute to communication between connected networks during executive functioning. To understand the functional role of neural synchrony in cognitive flexibility, we recorded from auditory cortex (AC) and medial prefrontal cortex (mPFC), while mice performed an auditory extinction learning task. We found that while animals gradually showed reduced responding to the unrewarded tone over hundreds of trials, the power of local field potential (LFP) oscillations (8-18 Hz, centered at alpha/beta frequencies) in AC and mPFC exhibited immediate and robust increases, prior to behavioral changes. The strength of LFP alpha/beta power in the mPFC, but not AC, was strongly correlated with the behavioral performance that mice would achieve later in the training session. Further, we found that coherence between AC and mPFC at 8-18Hz was selectively enhanced only after mice learned to suppress licking, and this LFP coherence increase coincided with a reduction ...

Cortical representations underlying a wide range of cognitive abilities, which employ both rate a... more Cortical representations underlying a wide range of cognitive abilities, which employ both rate and spike timing-based coding, emerge from underlying cortical circuits with a tremendous diversity of cell types. However, cell-type specific contributions to cortical coding are not well-understood. Here, we investigate the role of parvalbumin (PV) neurons in cortical complex scene analysis. Many complex scenes contain sensory stimuli, e.g., natural sounds, images, odors or vibrations, which are highly dynamic in time, competing with stimuli at other locations in space. PV neurons are thought to play a fundamental role in sculpting cortical temporal dynamics; yet their specific role in encoding complex scenes via timing-based codes, and the robustness of such temporal representations to spatial competition, have not been investigated. Here, we address these questions in auditory cortex using a cocktail party-like paradigm; integrating electrophysiology, optogenetic manipulations, and a ...

The Journal of Neuroscience, Sep 26, 2012

Nature Precedings, Oct 14, 2011

REM sleep enhances hippocampus-dependent associative memory but has little impact on striatal-dep... more REM sleep enhances hippocampus-dependent associative memory but has little impact on striatal-dependent procedural learning 1-3. Antidepressant medications like desipramine (DMI) inhibit rapid-eye-movement (REM) sleep but it is little understood how antidepressant treatments affect learning. We found that DMI strongly suppressed REM sleep in rats for several hours and impaired reconsolidation of a familiar maze and consolidation of moved baited positions (reversal learning) in a sleep-dependent fashion. Unexpectedly, DMI also reduced the spindle-rich transitionto-REM sleep state (TR) and spatial memory changes were more related to TR than to REM sleep. Working memory was unaffected, but overnight reference memory was significantly impaired and subjects increased reliance on non-hippocampal strategies. Procedural memory performance was positively correlated with increases in non-REM sleep after DMI serving to offset memory declines, partially preserving performance. Our results suggest that familiar memories are reconsolidated during REM sleep, reversal memories consolidated during TR, and procedural memories consolidated during non-REM sleep.

Scientific reports, Jan 8, 2016

Advances in neurotechnology have been integral to the investigation of neural circuit function in... more Advances in neurotechnology have been integral to the investigation of neural circuit function in systems neuroscience. Recent improvements in high performance fluorescent sensors and scientific CMOS cameras enables optical imaging of neural networks at a much larger scale. While exciting technical advances demonstrate the potential of this technique, further improvement in data acquisition and analysis, especially those that allow effective processing of increasingly larger datasets, would greatly promote the application of optical imaging in systems neuroscience. Here we demonstrate the ability of wide-field imaging to capture the concurrent dynamic activity from hundreds to thousands of neurons over millimeters of brain tissue in behaving mice. This system allows the visualization of morphological details at a higher spatial resolution than has been previously achieved using similar functional imaging modalities. To analyze the expansive data sets, we developed software to facili...

Nature, 2004

some similarity values were equal to zero (that is, no OTUs in common), we coded the similarity d... more some similarity values were equal to zero (that is, no OTUs in common), we coded the similarity data by adding 0.01 before log transforming each value 29. The approach outlined in ref. 14 allowed us to use relative comparisons of bacterial community composition rather than richness to examine the taxa-area relationship; richness is very difficult to estimate accurately in hyperdiverse communities such as bacterial communities. There is no reason to believe that undersampling and/or PCR biases will co-vary with intersample distance or will result in preferential sampling of those taxa most likely to be shared among samples located close together in space; thus, these factors, although likely to be present, are unlikely to influence the z-values we observed. In addition, we can think of no model in which PCR biases and/or undersampling could generate a taxa-area relationship that was completely artefactual. We compared the z-values for different taxon definitions by testing if the slopes of the regressions differed (see Supplementary Methods 2). We used the same distance decay approach to determine the z-value for plants, using data from the transect quadrants. Influence of habitat heterogeneity We used partial Mantel tests (9,999 permutations) to examine the influence of abiotic factors and aboveground plant composition on bacterial community composition, while holding geographic distance constant and vice versa. We constructed a distance matrix for plant community composition from per cent cover estimates for the four dominant species (Spartina alterniflora, Spartina patens, Salicornia virginica and Limonium nashii). We constructed a matrix of environmental distance from the abiotic factors identified as most important to community composition (phosphate and ammonia concentrations), using BIO-ENV 28. The BIO-ENV procedure selects a subset of available abiotic variables to maximize rank correlation between community similarity and abiotic dissimilarity matrices. We then used these matrices to test for additional distance and plant effects.

Neurobiology of learning and memory, Jan 18, 2016

In addition to the neuromodulatory role of cholinergic systems, brief, temporally discrete cholin... more In addition to the neuromodulatory role of cholinergic systems, brief, temporally discrete cholinergic release events, or "transients", have been associated with the detection of cues in attention tasks. Here we review four main findings about cholinergic transients during cognitive processing. Cholinergic transients are: (1) associated with the detection of a cue and influenced by cognitive state; (2) not dependent on reward outcome, although the timing of the transient peak co-varies with the temporal relationship between detection and reward delivery; (3) correlated with the mobilization of the cue-evoked response; (4) causal mediators of shifts from monitoring to cue detection. We next discuss some of the key questions concerning the timing and occurrence of transients within the framework of available evidence including: (1) Why does the shift from monitoring to cue detection require a transient? (2) What determines whether a cholinergic transient will be generated? (...

In loving memory of Howard Earl Gritton My father passed far too early but I feel his presence ev... more In loving memory of Howard Earl Gritton My father passed far too early but I feel his presence everyday of my life and I thank him for his guidance, wisdom, and love. iii Acknowledgements My time at Michigan has been filled with both struggle and success. I have made new friends, grown older and hopefully wiser, gotten married, and had my first child. I will always look back on this time in my life with a great deal of fondness and appreciation. Since my first days of graduate school, I have received a great deal of support, help, and encouragement from the University, from the outstanding faculty, and countless undergraduates, graduate students, post-doc's and support staff. The research presented in this dissertation is a collection of the efforts of many beyond my own and they deserve my sincere thanks and praise. In particular I would like to thank the Lee lab members

We present a single-shot multiplane widefield imaging strategy using a z-splitter prism, which ca... more We present a single-shot multiplane widefield imaging strategy using a z-splitter prism, which can be assembled from off-the-self components and only requires a single camera. We further introduce a novel extended-volume 3D deconvolution strategy to suppress far-out-of-focus fluorescence background to significantly improve the contrast of our recorded images, conferring to our system a capacity for quasi optical sectioning. By swapping in different z-splitter configurations, we can prioritize high speed or large 3D field-of-view imaging depending on the application of interest. Moreover, our system can be readily applied to a variety of imaging modalities in addition to fluorescence, such as phase-contrast and darkfield imaging, making it a versatile tool for a wide range of biological or biomedical imaging applications.

Biomedical Optics Express

The inherent constraints on resolution, speed and field of view have hindered the development of ... more The inherent constraints on resolution, speed and field of view have hindered the development of high-speed, three-dimensional microscopy techniques over large scales. Here, we present a multiplane line-scan imaging strategy, which uses a series of axially distributed reflecting slits to probe different depths within a sample volume. Our technique enables the simultaneous imaging of an optically sectioned image stack with a single camera at frame rates of hundreds of hertz, without the need for axial scanning. We demonstrate the applicability of our system to monitor fast dynamics in biological samples by performing calcium imaging of neuronal activity in mouse brains and voltage imaging of cardiomyocytes in cardiac samples.

Fast, volumetric imaging over large scales has been a long-standing challenge in biological micro... more Fast, volumetric imaging over large scales has been a long-standing challenge in biological microscopy. To address this issue, we developed a variant of confocal microscopy that provides simultaneous multiplane imaging over large field of view and at video rate. Our apparatus, called multi-Z confocal microscopy, differs from a conventional confocal microscope in both its illumination and detection parts. First, axially elongated illumination is achieved by under filling the back aperture of the microscope objective. The resulting low NA provides an axial extent of the illumination of the order of 100 µm. The light from the sample is then collected by the same objective, now taking advantage of the full NA which ensures high collection efficiency, and send to the detection unit. The latter is comprised by four reflecting pinholes axially distributed in the image plane such that they are conjugated to different depths within the sample. Each detection channel spans a probe volume at a...

Recent improvements in genetically encoded voltage indicators enabled optical imaging of action p... more Recent improvements in genetically encoded voltage indicators enabled optical imaging of action potentials and subthreshold membrane voltage dynamics from single neurons in the mammalian brain. To perform high speed voltage imaging, widefield microscopy remains an essential tool for recording activity from many neurons simultaneously over a large anatomical area. However, the lack of optical sectioning makes widefield microscopy more prone to background signal contamination, and thus far voltage imaging using fully genetically encoded voltage indicators remains limited to simultaneous sampling of a few cells over a restricted field-of-view. We here demonstrate a strategy for large scale voltage imaging using the fully genetically encoded voltage indicator SomArchon and targeted illumination. We implemented a simple, low-cost digital micromirror device based targeted illumination strategy to restrict illumination to the cells of interest, and systematically quantified the improvement...

Cortical synchrony is theorized to contribute to communication between connected networks during ... more Cortical synchrony is theorized to contribute to communication between connected networks during executive functioning. To understand the functional role of neural synchrony in cognitive flexibility, we recorded from auditory cortex (AC) and medial prefrontal cortex (mPFC), while mice performed an auditory extinction learning task. We found that while animals gradually showed reduced responding to the unrewarded tone over hundreds of trials, the power of local field potential (LFP) oscillations (8-18 Hz, centered at alpha/beta frequencies) in AC and mPFC exhibited immediate and robust increases, prior to behavioral changes. The strength of LFP alpha/beta power in the mPFC, but not AC, was strongly correlated with the behavioral performance that mice would achieve later in the training session. Further, we found that coherence between AC and mPFC at 8-18Hz was selectively enhanced only after mice learned to suppress licking, and this LFP coherence increase coincided with a reduction ...

Cortical representations underlying a wide range of cognitive abilities, which employ both rate a... more Cortical representations underlying a wide range of cognitive abilities, which employ both rate and spike timing-based coding, emerge from underlying cortical circuits with a tremendous diversity of cell types. However, cell-type specific contributions to cortical coding are not well-understood. Here, we investigate the role of parvalbumin (PV) neurons in cortical complex scene analysis. Many complex scenes contain sensory stimuli, e.g., natural sounds, images, odors or vibrations, which are highly dynamic in time, competing with stimuli at other locations in space. PV neurons are thought to play a fundamental role in sculpting cortical temporal dynamics; yet their specific role in encoding complex scenes via timing-based codes, and the robustness of such temporal representations to spatial competition, have not been investigated. Here, we address these questions in auditory cortex using a cocktail party-like paradigm; integrating electrophysiology, optogenetic manipulations, and a ...