Neuroscience and Cognitive Science

Decoding three-dimensional hand kinematics from electroencephalographic signals


Authors: Trent J. Bradberry, Rodolphe J. Gentili, José L. Contreras-Vidal
Department or Program: BIOE
Presented by: Trent Bradberry
Abstract: The capacity to decode kinematics of intended movement from neural activity is necessary for the development of neuromotor prostheses such as smart artificial arms. Thus far, most of the progress in the development of neuromotor prostheses has been achieved by decoding kinematics of the hand from intracranial neural activity. The comparatively low signal-to-noise ratio and spatial resolution of neural data acquired non-invasively from the scalp via electroencephalography (EEG) have been presumed to prohibit the extraction of detailed information about hand kinematics. Here, we challenge this presumption by attempting to continuously decoding hand position, velocity, and acceleration from 55-channel EEG signals acquired during three-dimensional center-out reaching from five subjects. To preserve ecological validity, reaches were self-initiated, and targets were self-selected. After cross-validation, the overall mean correlation coefficients between measured and reconstructed position, velocity, and acceleration were 0.2, 0.3, and 0.3 respectively. These modest results support the continued development of non-invasive neuromotor prostheses for movement-impaired individuals.

Role of Ca2+ permeable AMPA receptors in visual cortex synaptic plasticity following brief visual deprivation


Authors: Kevin M. McGehrin, Dr. Hey-Kyoung Lee
Department or Program: BIOL
Presented by: Kevin McGehrin
Abstract: Neurons change in function and physical structure at their synapses in order to store new memories in our brains. This change is termed synaptic plasticity, and is studied using two different models: long-term potentiation (LTP), a prolonged increase in synaptic transmission, and long-term depression (LTD), a persistent decrease in synaptic transmission. Changes at synapses are regulated and balanced by homeostatic mechanisms, one of which is synaptic scaling. Synaptic scaling keeps neuronal activity in a functional range by either increasing or decreasing synaptic strength accordingly. In the visual cortex, this is mainly due to regulation of synaptic AMPA receptor function by changes in subunit composition, which affects Ca2+ permeability. Recently, it has been shown that dark-rearing mice for two days is sufficient for scaling up synapses in the visual cortex. However, the functional consequence of this is unknown. Dark-rearing from birth has been shown to increase the magnitude of LTP and decrease the magnitude of LTD, which is mainly due to the developmental arrest of NMDA receptors and inhibitory function. We hypothesize that synaptic scaling by a shorter duration of dark-rearing following normal development will alter the magnitudes of LTP and LTD mainly by regulating the Ca2+ permeability of AMPA receptors.

Characterization of visual experience-induced homeostatic synaptic plasticity in layer 6 pyramidal neurons of mouse visual corte


Authors: Terence Anguh, Huy Pho, Hui Wang, Angela Lee, Emily Petrus and Hey-Kyoung Lee
Department or Program: BIOL
Presented by: Terence Anguh
Abstract: Input-specific changes in visual cortex circuitry are thought to happen via synapse-specific plasticity mechanisms, such as long-term potentiation (LTP) and long-term depression (LTD). While synapse-specific plasticity is a powerful mechanism to sculpt neural circuits by activity, it has been recognized early on that such plasticity mechanisms are inherently unstable, and therefore require an additional layer of homeostatic regulation to provide stability. In order to keep the system stable, homeostatic plasticity mechanisms also have to be regulated by activity driven by visual experience. We have previously shown that 2 days of visual deprivation in the form of dark-rearing (from P21 to P23) can globally scale up the amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in layer 2/3 of the mouse visual cortex. Interestingly, these changes were not just restricted to early development, but can be induced even in adults (P97) (Goel and Lee, 2007). On the other hand, layer 4 synaptic scaling by 2 days of visual deprivation is reported to be restricted to an early critical period (P14-P16) (Desai et al., 2002). These findings suggest that different layers of the visual cortex respond differently to visual deprivation depending on the developmental age of an animal. Our study was designed to examine visual deprivation-induced synaptic changes in layer 6 pyramidal cells. These neurons receive thalamocortical inputs like layer 4, but are different in that they also provide feedback projections to the lateral geniculate nucleus (LGN). We report that 2 days of dark-rearing from P21-P23 does not significantly alter AMPA receptor-mediated mEPSC amplitude (normal-reared = 13.1 ± 1.0 pA; dark-reared = 13.4 ± 1.6 pA; n = 5 each) or frequency (normal-reared = 1.2 ± 0.4 Hz; dark-reared = 1.4 ± 0.3 Hz; n = 5 each) in layer 6 neurons. We are currently looking at younger ages to see whether layer 6 has a similar early critical period as layer 4.

Mapping the connectivity of neurons in primary visual cortex of mice


Authors: Cara Jacobs, Ming Gao, and Hey-Kyoung Lee
Department or Program: NACS
Presented by: Cara Jacobs
Abstract: Connectivity of neurons in the brain is critical for mediating proper function. In the primary sensory cortices of higher mammals, it is well documented that neurons are organized in a columnar fashion. It has been discovered more recently that the axonal arbor of layer 4 spiny neurons overlap considerably with the dendritic "receptive" fields of the  layer 2/3 pyramidal cell in the somatosensory cortex of rodents. Unlike in cats and primates, the visual cortex of rodents is not functionally  organized in a well defined columnar manner. Therefore, we want to examine the connectivity profile of layer 4 stellate and star pyramids to layer 2/3 pyramidal neurons in the mouse visual cortex. To do this, we will perform 3 dimensional reconstruction of confocal images of biocytin filled neurons. From these images, we will calculate the connection probability between layer 4 and layer 2/3, as well as the topological organization of the connected neuronal pairs. Furthermore, we will investigate whether the connectivity profile can be modulated by changes in visual experience. As a first step, we show that processing biocytin filled neurons with fluorescently labeled streptavidin is a viable method for obtaining a 3 dimensional image of neurons. Once a synaptically connected pair of neurons is found through electrophysiological methods, we will then determine their connectivity map.  Mapping the connectivity of these neurons is crucial, as this will provide a better understanding of the fuctional curcuit in the primary visual cortex of mice.


Mossy fiber LTP deficits in BACE1 knockouts can be rescued by activation of α7 nicotinic acetylcholine receptors


Authors: Hui Wang, Philip C. Wong, Hey-Kyoung Lee
Department or Program: NACS
Presented by: Hui Wang
Abstract: Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), the β-secretase required for the formation of β-amyloid (Aβ) peptides, is thought to be one of the key therapeutic targets that can prevent the progression of Alzheimer’s disease (AD). Although complete ablation of BACE1 gene prevents Aβ formation, our previous study showed that BACE1 knockout mice display severe presynaptic deficits at mossy fiber to CA3 synapses in hippocampus, one of the major loci of BACE1 expression in the brain, and such deficits are likely due to abnormal presynaptic Ca2+ regulation. Cholinergic system has been implicated in several neurodegenerative disorders including AD, in some cases via activation of nicotinic acetylcholine receptors (nAChRs), among which are Ca2+ permeable α7-nAChRs. Here we present data that brief application of nicotine at mossy fiber to CA3 synapses can restore presynaptic release (as measured by a significantly decrease in paired-pulse facilitation (PPF) ratio) and rescue mossy fiber LTP in BACE1 knockouts. This effect was blocked by α-bungarotoxin, an antagonist of α7-nAChRs, and mimicked by a specific agonist of α7-nAChRs PNU 282987. Our data suggest that nicotine can recover the presynaptic deficits in BACE1 knockouts at mossy fiber to CA3 synapses by activating α7-nAChRs.

Cholinergic modulation of reciprocal synapses in the accessory olfactory bulb


Authors: Richard S. Smith and Ricardo C. Araneda
Department or Program: BIOL
Presented by: Richard Smith
Abstract: The accessory olfactory bulb (AOB) is the first relay of chemosensory information important for sexual and aggressive behaviors. Neuromodulation of reciprocal synapses between the output neurons (mitral/tufted cells; MCs) and inhibitory interneurons (granule cells; GCs) by afferent fibers of the cholinergic system is thought to play an important role in olfactory processing in the bulb. Here, using an in vitro slice preparation we have characterized the effects of cholinergic activation on neuronal excitability in the AOB. We found that activation of muscarinic acetylcholine receptors (mAChRs) increases the overall activity at reciprocal synapses between MCs and GCs. The non-selective muscarinic agonist oxotremorine (30 uM) increases excitability of GCs by three mechanisms; a long lasting depolarization, activation of a slow afterdepolarization (sADP) in response to stimulation of the cells and an increase in excitatory glutamatergic input onto GCs. Pharmacological dissection of these effects indicated that the depolarization and the sADP are mediated by activation of M1 mAChRs, as these responses are elicited by the selective M1 agonist MCN-A-343 (100 uM) and blocked by pirenzepine (300 nM), a selective M1 antagonist. In addition, we find that cholinergic agonists elicited a depolarization of MCs via two different mechanisms, activation of M1 mAChRs and nicotinic AChRs. Our results indicate that muscarinic receptor activation promotes bidirectional activation of reciprocal synapses in the AOB.

Adult Neurogenesis in the accessory olfactory bulb


Authors: Alexia Nunez-Parra and Ricardo C. Araneda
Department or Program: NACS
Presented by: Alexia Nunez
Abstract: The two regions of the mouse olfactory system, the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), play a complementary role in the processing of chemosensory information related to social and sexual behavior. Furthermore, the olfactory bulb is one of the few regions that exhibit adult neurogenesis, which has been extensively characterized in the MOB and has been shown to vary under different physiological conditions. Most newly born cells in the adult mature into granule inhibitory neurons and are functionally integrated into the existing neuronal network. Little is known, however, about the role and extent of adult neurogenesis in the AOB and whether it can be regulated by behavior as in the MOB. Here, using immunohistochemical techniques and BrdU to label newly born cells, we determined the extent of adult neurogenesis in mice AOB. We found abundant labeled cells in the granule cell (GC) layer of the mouse AOB (3494±591 and 2611±337 BrdU+cells/mm3, male and female mice respectively) at one month of age. We also observed a dramatic decrease in adult neurogenesis in two month old animals of both sexes in all the different layers of the AOB (i.e 1090±91 and 1842±161 BrdU+cells/mm3 in the GC layer of male and female mice respectively). In addition, we studied adult neurogenesis modulation by exposing sexually naive adult females to soil bedding odorized by a male or female and quantified newly born cells. We found that BrdU+cells were significantly increased in the GC layer of the posterior AOB in odor exposed females (2480±226 v/s 1275±112; p<0.05). Moreover, we quantified the number of newly born neurons after males were confronted and aggressive behavior was elicited through the resident-intruder paradigm. Compared with control mice, subordinates and residents showed an increased in neurogenesis in the GC layer of the anterior AOB (1365±540 v/s 2288±365 and 2593±208 BrdU+cells/mm3, control, resident and intruder respectively; p<0.05). These results indicate that the AOB exhibits considerable neurogenesis that can be differentially regulated in the AOB by odor exposure and aggression, suggesting an important role of adult neurogenesis in social behaviors.

Male general cognitive ability influences male mating success in the satin bowerbird


Authors: Jason Kagy, Jean-Francois Savard, and Gerald Borgia
Department or Program: BEES
Presented by: Jason Keagy
Abstract: The findings that song complexity is related to learning ability, song quality is related to male reproductive success, and males adjust their behavior according to female signals points to a likely relationship between general cognitive performance and reproductive success. The ‘cognitive performance hypothesis’ posits that individuals demonstrating greater general cognitive performance are preferred in mate choice. Satin bowerbirds (Ptilonorhynchus violaceus) are an excellent species for testing this hypothesis because their complex male courtship, including bower building and mimicry of other species of birds, suggests a selective advantage to individuals with higher cognitive abilities. We assessed 21 males for performance on an array of cognitive tasks including problem-solving ability, bower building ability, and mimetic ability. In addition, we used canonical correlation analysis to construct an analog to the human intelligence factor, g, and compared this ‘bowerbird g’ to male mating success. Problem-solving ability and mimetic ability each predicted mating success. In addition, our bowerbird g score significantly correlated with mating success. Our findings suggest that males with better general cognitive performance are more sexually attractive.

Determining Nicotinic Acetylcholine Receptor Presence in Mossy Fiber Synapses Using Immunohistochemistry


Authors: Angela Lee, Hui Wang, and Hey-Kyoung Lee
Department or Program: BIOL
Presented by: Angela Lee
Abstract: Alzheimer’s disease (AD) is a serious neurological disorder that usually begins with the loss of ability to encode new memories. At the heart of AD pathology is amyloid beta (Abeta) peptides that disrupt synaptic plasticity, an important mechanism for memory formation. Blocking BACE1, one of the enzymes critical for the formation of Abeta peptides, has emerged as a promising therapeutic target. However, inhibiting BACE1 expression in mice results in cognitive and emotional deficits in behavior as well as synaptic plasticity. We recently found that nicotinic acetylcholine receptor (nAchR) activation can rescue the synaptic deficits found in BACE1 knockout mice. In order to better determine the mechanism underlying the action of nicotine, we examined the expression pattern of nAchRs in the hippocampus through immunohistochemical staining of mouse hippocampal slices. Data from our study will aid in the development of better therapeutics targeting BACE1 for the treatment of Alzheimer's disease.

Lesser Scaup Audiograms


Authors: Sara C. Therrien, Ronald E. Therrien, Catherine E. Carr et al.
Department or Program: NACS
Presented by: Sara Therrien
Abstract: Humans have an increasing presence in waterways all over the world. Increases in anthropogenic sources of noise, such as underwater construction, explosives, military sonars, and commercial and recreational vessels, have the potential to interrupt signal transmission in all animals that use acoustic energy in the water. However, in order to assess this risk, the sensory biology of diving animals must first be investigated. Currently, little is known about the hearing abilities and vocal behavior of diving birds while underwater. In this study, underwater auditory thresholds of Lesser Scaup (Aythya affinis), a species of diving duck, will be estimated using several methods. Preliminary results from the auditory brainstem response (ABR) in air suggest that Lesser Scaup have maximum sensitivity at about 2000 Hz. Birds are currently being trained to participate in a behavioral audiogram to determine their thresholds underwater. When thresholds are obtained, it will be possible to compare hearing abilities in air and underwater, and look for any adaptations for using acoustic energy in the water.

Activity-dependent recovery from short-term synaptic depression in the avian cochlear nucleus


Authors: Katrina MacLeod and Timothy Horiuchi
Department or Program: BIOL
Presented by: Katrina MacLeod
Abstract: Short-term synaptic plasticity acts as a time- and firing rate-dependent filter that mediates the transmission of information across synapses. In the auditory brainstem, specific forms of plasticity are expressed at different terminals of the same auditory nerve fibers and contribute to the divergence of acoustic timing and intensity information into separate, parallel computation pathways. Using whole-cell patch clamp recordings of postsynaptic currents in the avian cochlear nucleus, we demonstrate that these synapses have a very rapid recovery from depression, explaining their ability to maintain responses during high rates of spontaneous and sensory driven activity. The rate of recovery showed a dependence on the presynaptic activity levels. In both the intensity and timing pathways, the time course of recovery from short-term depression was bi-exponential, with a fast time constant of ~40 ms, explaining ~80% of the recovery, and a slow time constant on the order of several seconds. In the intensity pathway, the fast recovery was not due to postsynaptic receptor desensitization, and was complicated by the presence of short-term facilitation that may partially contribute to the rapid time course of recovery. A cascade model of synaptic vesicle replenishment is described that accounts for the activity-dependence and time course of the recovery without requiring residual calcium feedback. The simple model of presynaptic short-term plasticity presented here provides an unexpected explanation for activity-dependent recovery and illustrates the dynamic nature of vesicle cycling.

A Neuromorphic Head Direction Cell System


Authors: Tarek M. Massoud, Timothy K. Horiuchi
Department or Program: ENEE
Presented by: Tarek Massoud
Abstract: The head direction (HD) cell system in the brain of mammals is thought to be part of the neural circuitry supporting their spatial navigation capabilities. In this paper we present a neuromorphic VLSI system that mimics the operation of the HD system. Relying on spiking neurons and attractor dynamics, this system can be used to represent and retain the current estimate of head orientation in the environment and integrate angular velocity to update this estimate. The presented system is a first step towards more general odometry systems that could be used for modeling biological navigation systems.