Latest Articles Include:
- Location Matters: Synaptotagmin Helps Place Vesicles Near Calcium Channels
McNeil BD Wu LG - Neuron 63(4):419-421 (2009)
Positioning releasable vesicles near voltage-gated calcium channels may ensure transmitter release upon calcium influx. Disruption of vesicle positioning may underlie short-term synaptic depression. However, how this positioning is achieved is unclear. In this issue of Neuron, Young and Neher find that synaptotagmin 2 helps to align readily releasable vesicles near calcium channels at nerve terminals. - Imagining the Possibilities: Ripples, Routes, and Reactivation
Knierim JJ - Neuron 63(4):421-423 (2009)
Hippocampal place cells fire selectively when a rat occupies a particular location. Under certain conditions, the cells briefly represent trajectories along locations away from the rat's current location. New results lend important insight into this phenomenon and demonstrate spatiotemporally coherent, cognitive representations that are independent of current sensory input. - Harnessing Chaos in Recurrent Neural Networks
Buonomano DV - Neuron 63(4):423-425 (2009)
In this issue of Neuron, Sussillo and Abbott describe a new learning rule that helps harness the computational power of recurrent neural networks. - The Neurobiological Basis of Posttraumatic Stress Disorder and Its Treatment
- Neuron 63(4):426-428 (2009)
- Supraresolution Imaging in Brain Slices using Stimulated-Emission Depletion Two-Photon Laser Scanning Microscopy
Ding JB Takasaki KT Sabatini BL - Neuron 63(4):429-437 (2009)
Two-photon laser scanning microscopy (2PLSM) has allowed unprecedented fluorescence imaging of neuronal structure and function within neural tissue. However, the resolution of this approach is poor compared to that of conventional confocal microscopy. Here, we demonstrate supraresolution 2PLSM within brain slices. Imaging beyond the diffraction limit is accomplished by using near-infrared (NIR) lasers for both pulsed two-photon excitation and continuous wave stimulated emission depletion (STED). Furthermore, we demonstrate that Alexa Fluor 594, a bright fluorophore commonly used for both live cell and fixed tissue fluorescence imaging, is suitable for STED 2PLSM. STED 2PLSM supraresolution microscopy achieves approximately 3-fold improvement in resolution in the radial direction over conventional 2PLSM, revealing greater detail in the structure of dendritic spines located 100 microns below the surface of brain slices. Further improvements in resolution are theoreticall! y achievable, suggesting that STED 2PLSM will permit nanoscale imaging of neuronal structures located in relatively intact brain tissue. - Spontaneous Generation of Prion Infectivity in Fatal Familial Insomnia Knockin Mice
Jackson WS Borkowski AW Faas H Steele AD King OD Watson N Jasanoff A Lindquist S - Neuron 63(4):438-450 (2009)
A crucial tenet of the prion hypothesis is that misfolding of the prion protein (PrP) induced by mutations associated with familial prion disease is, in an otherwise normal mammalian brain, sufficient to generate the infectious agent. Yet this has never been demonstrated. We engineered knockin mice to express a PrP mutation associated with a distinct human prion disease, fatal familial insomnia (FFI). An additional substitution created a strong transmission barrier against pre-existing prions. The mice spontaneously developed a disease distinct from that of other mouse prion models and highly reminiscent of FFI. Unique pathology was transmitted from FFI mice to mice expressing wild-type PrP sharing the same transmission barrier. FFI mice were highly resistant to infection by pre-existing prions, confirming infectivity did not arise from contaminating agents. Thus, a single amino acid change in PrP is sufficient to induce a distinct neurodegenerative disease and the spo! ntaneous generation of prion infectivity. - Distinct Temporal Requirements for the Homeobox Gene Gsx2 in Specifying Striatal and Olfactory Bulb Neuronal Fates
Waclaw RR Wang B Pei Z Ehrman LA Campbell K - Neuron 63(4):451-465 (2009)
The homeobox gene Gsx2 (formerly Gsh2) is known to be required for striatal and olfactory bulb neurogenesis; however, its specific role in the specification of these two neuronal subtypes remains unclear. To address this, we have employed a temporally regulated gain-of-function approach in transgenic mice and found that misexpression of Gsx2 at early stages of telencephalic neurogenesis favors the specification of striatal projection neuron identity over that of olfactory bulb interneurons. In contrast, delayed activation of the Gsx2 transgene until later stages exclusively promotes olfactory bulb interneuron identity. In a complementary approach, we have conditionally inactivated Gsx2 in a temporally progressive manner. Unlike germline Gsx2 mutants, which exhibit severe alterations in both striatal and olfactory bulb neurogenesis at birth, the conditional mutants exhibited defects restricted to olfactory bulb interneurons. These results demonstrate that Gsx2 specifies! striatal projection neuron and olfactory bulb interneuron identity at distinct time points during telencephalic neurogenesis. - The Cell-Intrinsic Requirement of Sox6 for Cortical Interneuron Development
Batista-Brito R Rossignol E Hjerling-Leffler J Denaxa M Wegner M Lefebvre V Pachnis V Fishell G - Neuron 63(4):466-481 (2009)
We describe the role of Sox6 in cortical interneuron development, from a cellular to a behavioral level. We identify Sox6 as a protein expressed continuously within MGE-derived cortical interneurons from postmitotic progenitor stages into adulthood. Both its expression pattern and null phenotype suggests that Sox6 gene function is closely linked to that of Lhx6. In both Lhx6 and Sox6 null animals, the expression of PV and SST and the position of both basket and Martinotti neurons are abnormal. We find that Sox6 functions downstream ofLhx6. Electrophysiological analysis of Sox6 mutant cortical interneurons revealed that basket cells, even when mispositioned, retain characteristic but immature fast-spiking physiological features. Our data suggest that Sox6 is not required for the specification of MGE-derived cortical interneurons. It is, however, necessary for their normal positioning and maturation. As a consequence, the specific removal of Sox6 from this population res! ults in a severe epileptic encephalopathy. - Synaptotagmin Has an Essential Function in Synaptic Vesicle Positioning for Synchronous Release in Addition to Its Role as a Calcium Sensor
Young SM Neher E - Neuron 63(4):482-496 (2009)
A multitude of synaptic proteins interact at the active zones of nerve terminals to achieve the high temporal precision of neurotransmitter release in synchrony with action potentials. Though synaptotagmin has been recognized as the Ca2+ sensor for synchronous release, it may have additional roles of action. We address this question at the calyx of Held, a giant presynaptic terminal, that allows biophysical dissection of multiple roles of molecules in synaptic transmission. Using high-level expression recombinant adenoviruses, in conjunction with a stereotactic surgery in postnatal day 1 rats, we overcame the previous inability to moleculary perturb the calyx by overexpression of a mutated synaptotagmin. We report that this mutation leaves intrinsic Ca2+ sensitivity of vesicles intact while it destabilizes the readily releasable pool of vesicles and loosens the tight coupling between Ca2+ influx and release, most likely by interfering with the correct positioning of ve! sicles with respect to Ca2+ channels. - Hippocampal Replay of Extended Experience
Davidson TJ Kloosterman F Wilson MA - Neuron 63(4):497-507 (2009)
During pauses in exploration, ensembles of place cells in the rat hippocampus re-express firing sequences corresponding to recent spatial experience. Such "replay" co-occurs with ripple events: short-lasting (50–120 ms), high-frequency (200 Hz) oscillations that are associated with increased hippocampal-cortical communication. In previous studies, rats exploring small environments showed replay anchored to the rat's current location and compressed in time into a single ripple event. Here, we show, using a neural decoding approach, that firing sequences corresponding to long runs through a large environment are replayed with high fidelity and that such replay can begin at remote locations on the track. Extended replay proceeds at a characteristic virtual speed of 8 m/s and remains coherent across trains of ripple events. These results suggest that extended replay is composed of chains of shorter subsequences, which may reflect a strategy for the storage and flexib! le expression of memories of prolonged experience. - Direct Activation of Sparse, Distributed Populations of Cortical Neurons by Electrical Microstimulation
Histed MH Bonin V Reid RC - Neuron 63(4):508-522 (2009)
For over a century, electrical microstimulation has been the most direct method for causally linking brain function with behavior. Despite this long history, it is still unclear how the activity of neural populations is affected by stimulation. For example, there is still no consensus on where activated cells lie or on the extent to which neural processes such as passing axons near the electrode are also activated. Past studies of this question have proven difficult because microstimulation interferes with electrophysiological recordings, which in any case provide only coarse information about the location of activated cells. We used two-photon calcium imaging, an optical method, to circumvent these hurdles. We found that microstimulation sparsely activates neurons around the electrode, sometimes as far as millimeters away, even at low currents. Our results indicate that the pattern of activated neurons likely arises from the direct activation of axons in a volume tens! of microns in diameter. - MT Neurons Combine Visual Motion with a Smooth Eye Movement Signal to Code Depth-Sign from Motion Parallax
Nadler JW Nawrot M Angelaki DE DeAngelis GC - Neuron 63(4):523-532 (2009)
The capacity to perceive depth is critical for an observer to interact with his or her surroundings. During observer movement, information about depth can be extracted from the resulting patterns of image motion on the retina (motion parallax). Without extraretinal signals related to observer movement, however, depth-sign (near versus far) from motion parallax can be ambiguous. We previously demonstrated that MT neurons combine visual motion with extraretinal signals to code depth-sign from motion parallax in the absence of other depth cues. In that study, head translations were always accompanied by compensatory tracking eye movements, allowing at least two potential sources of extraretinal input. We now show that smooth eye movement signals provide the critical extraretinal input to MT neurons for computing depth-sign from motion parallax. Our findings demonstrate a powerful modulation of MT activity by eye movements, as predicted by human studies of depth perception! from motion parallax. - Activation of the Opioidergic Descending Pain Control System Underlies Placebo Analgesia
Eippert F Bingel U Schoell ED Yacubian J Klinger R Lorenz J Büchel C - Neuron 63(4):533-543 (2009)
Placebo analgesia involves the endogenous opioid system, as administration of the opioid antagonist naloxone decreases placebo analgesia. To investigate the opioidergic mechanisms that underlie placebo analgesia, we combined naloxone administration with functional magnetic resonance imaging. Naloxone reduced both behavioral and neural placebo effects as well as placebo-induced responses in pain-modulatory cortical structures, such as the rostral anterior cingulate cortex (rACC). In a brainstem-specific analysis, we observed a similar naloxone modulation of placebo-induced responses in key structures of the descending pain control system, including the hypothalamus, the periaqueductal gray (PAG), and the rostral ventromedial medulla (RVM). Most importantly, naloxone abolished placebo-induced coupling between rACC and PAG, which predicted both neural and behavioral placebo effects as well as activation of the RVM. These findings show that opioidergic signaling in pain-mo! dulating areas and the projections to downstream effectors of the descending pain control system are crucially important for placebo analgesia. - Generating Coherent Patterns of Activity from Chaotic Neural Networks
Sussillo D Abbott LF - Neuron 63(4):544-557 (2009)
Neural circuits display complex activity patterns both spontaneously and when responding to a stimulus or generating a motor output. How are these two forms of activity related? We develop a procedure called FORCE learning for modifying synaptic strengths either external to or within a model neural network to change chaotic spontaneous activity into a wide variety of desired activity patterns. FORCE learning works even though the networks we train are spontaneously chaotic and we leave feedback loops intact and unclamped during learning. Using this approach, we construct networks that produce a wide variety of complex output patterns, input-output transformations that require memory, multiple outputs that can be switched by control inputs, and motor patterns matching human motion capture data. Our results reproduce data on premovement activity in motor and premotor cortex, and suggest that synaptic plasticity may be a more rapid and powerful modulator of network activi! ty than generally appreciated.
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