Faculty Bibliography

Change history: In this Letter, the Acknowledgements section should have included the following sentence: "The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.". This omission has been corrected online.

Massive galaxy clusters have been found that date to times as early as three billion years after the Big Bang, containing stars that formed at even earlier epochs^1-3. The high-redshift progenitors of these galaxy clusters-termed 'protoclusters'-can be identified in cosmological simulations that have the highest overdensities (greater-than-average densities) of dark matter^4-6. Protoclusters are expected to contain extremely massive galaxies that can be observed as luminous starbursts ⁷ . However, recent detections of possible protoclusters hosting such starbursts^8-11 do not support the kind of rapid cluster-core formation expected from simulations ¹² : the structures observed contain only a handful of starbursting galaxies spread throughout a broad region, with poor evidence for eventual collapse into a protocluster. Here we report observations of carbon monoxide and ionized carbon emission from the source SPT2349-56. We find that this source consists of at least 14 gas-rich galaxies, all lying at redshifts of 4.31. We demonstrate that each of these galaxies is forming stars between 50 and 1,000 times more quickly than our own Milky Way, and that all are located within a projected region that is only around 130 kiloparsecs in diameter. This galaxy surface density is more than ten times the average blank-field value (integrated over all redshifts), and more than 1,000 times the average field volume density. The velocity dispersion (approximately 410 kilometres per second) of these galaxies and the enormous gas and star-formation densities suggest that this system represents the core of a cluster of galaxies that was already at an advanced stage of formation when the Universe was only 1.4 billion years old. A comparison with other known protoclusters at high redshifts shows that SPT2349-56 could be building one of the most massive structures in the Universe today.

The unipolar brush cell (UBC) is a glutamatergic granular layer interneuron that is predominantly located in the vestibulocerebellum and parts of the vermis. In rat and rabbit, we previously found using juxtacellular labeling combined with spontaneous activity recording that cells with highly regular spontaneous activity belong to the UBC category. Making use of this signature, we recorded from floccular UBCs in both anesthetized and awake rabbits while delivering visuo-vestibular stimulation by using sigmoidal rotation of the whole animal. In the anesthetized rabbit, the activity of the presumed UBC units displayed a wide variety of modulation profiles that could be related to aspects of head velocity or acceleration. These modulation profiles could also be found in the awake rabbit where, in addition, they could also carry an eye position signal. Furthermore, units in the awake rabbit could demonstrate rather long response latencies of up to 0.5 s. We suggest that the UBCs recorded in this study mostly belong to the type I UBC category (calretinin-positive) and that they can play diverse roles in floccular visuo-vestibular information processing, such as transformation of velocity-related signals to acceleration-related signals.

BACKGROUND: We have extended our cerebellar cortical interneuron classification algorithm that uses statistics of spontaneous activity (Ruigrok et al., 2011) to include Purkinje cells. Purkinje cells were added because they do not always show a detectable complex spike, which is the accepted identification. The statistical measures used in the present study were obtained from morphologically identified interneurons and complex spike identified Purkinje cells, recorded from ketamine-xylazine anesthetized rats and rabbits, and from awake rabbits. NEW METHOD: The new algorithm has an added decision step that classifies Purkinje cells using a combination of the median absolute difference from the median interspike interval (MAD) and the mean of the relative differences of successive interspike intervals (CV2). These measures reflect the high firing rate and intermediate regularity of Purkinje cell simple spike activity. RESULTS: Of 86 juxtacellularly labeled interneurons and 110 complex spike-identified Purkinje cells, 61 interneurons and 95 Purkinje cells were correctly classified, 22 interneurons and 13 Purkinje cells were deemed unclassifiable, and 3 interneurons and 2 Purkinje cells were incorrectly classified. COMPARISON WITH EXISTING METHODS: The new algorithm improves on our previous algorithm because it includes Purkinje cells. This algorithm is the only one for the cerebellum that does not presume anatomical knowledge of whether the cells are in the molecular layer or the granular layer. CONCLUSIONS: These results strengthen the view that the new decision algorithm is useful for identifying neurons recorded at all cerebellar depths, particularly those neurons recorded in the rabbit vestibulocerebellum.

In addition to the well-known signals of retinal image slip, floccular complex spikes (CSs) also convey nonvisual signals. We recorded eye movement and CS activity from Purkinje cells in awake rabbits sinusoidally oscillated in the dark on a vestibular turntable. The stimulus frequency ranged from 0.2 to 1.2 Hz, and the velocity amplitude ranged from 6.3 to 50 degrees /s. The average CS modulation was evaluated at each combination of stimulus frequency and amplitude. More than 75% of the Purkinje cells carried nonvisual CS signals. The amplitude of this modulation remained relatively constant over the entire stimulus range. The phase response of the CS modulation in the dark was opposite to that during the vestibulo-ocular reflex (VOR) in the light. With increased frequency, the phase response systematically shifted from being aligned with contraversive head velocity toward peak contralateral head position. At fixed frequency, the phase response was dependent on peak head velocity, indicating a system nonlinearity. The nonvisual CS modulation apparently reflects a competition between eye movement and vestibular signals, resulting in an eye movement error signal inferred from nonvisual sources. The combination of this error signal with the retinal slip signal in the inferior olive results in a net error signal reporting the discrepancy between the actual visually measured eye movement error and the inferred eye movement error derived from measures of the internal state. The presence of two error signals requires that the role of CSs in models of the floccular control of VOR adaption be expanded beyond retinal slip.

The contention of this commentary, focused on the vestibulocerebellum (particularly the flocculus), is that the great importance for our understanding of cerebellar organization in terms of climbing fiber zones, begun years ago by Voogd [1969, 2011] and Oscarsson [1969], needs to be matched by coming more to grips with the other fundamental geometrical organization of the cerebellum, the parallel fibers. The central issue is the selection of those parallel fiber signals to be transformed into Purkinje cell activity in the different zones. At present, in comparison to our knowledge of vestibulocerebellar climbing fiber inputs, the deficiencies in our knowledge of the zonal anatomy and physiology of vestibulocerebellar mossy fibers and granule cells are glaring. The recent emphasis on molecularly oriented investigations points to the need to reinvigorate pursuit of unanswered questions about cerebellar anatomy, the handmaiden of physiology

Cerebellar cortical interneurons such as Golgi cells, basket cells, stellate cells, unipolar brush cells, and granule cells play an essential role in the operations of the cerebellum. However, detailed functional studies of the activity of these cells in both anesthetized and behaving animals have been hampered by problems in recognizing their physiological signatures. We have extracellularly recorded the spontaneous activity of vestibulocerebellar interneurons in ketamine/xylazine-anesthetized rats and subsequently labeled them with Neurobiotin using the juxtacellular technique. After recovery and morphological identification of these cells, they were related to statistical measures of their spontaneous activity. Golgi cells display a somewhat irregular firing pattern with relatively low average frequencies. Unipolar brush cells are characterized by more regular firing at higher rates. Basket and stellate cells are alike in their firing characteristics, which mainly stand out by their irregularity; some of them are set apart by their very slow average rate. The spontaneous activity of interneurons examined in the ketamine/xylazine rabbit fit within this general pattern. In the rabbit, granule cells were identified by the spontaneous occurrence of extremely high-frequency bursts of action potentials, which were also recognized in the rat. On the basis of these observations, we devised an algorithm that reliably determined the identity of 75% of the cells with only 2% incorrect classifications. The remaining cells were placed into border categories within which no classification was attempted. We propose that this algorithm can be used to help classify vestibulocerebellar interneurons recorded in awake, behaving animals

Whether ocular orientation to gravity is produced solely by linear acceleration in the horizontal plane of the head or depends on both horizontal and vertical components of the acceleration of gravity is controversial. Here, we compared orienting eye movements of rabbits during head tilt to those produced by centrifugation that generated centripetal acceleration along the naso-occipital (X-), bitemporal (Y-) and vertical (Z-) axes in a constant gravitational field. Sensitivities of ocular counter-pitch and vergence during pitch tilts were approximately 25 degrees /g and approximately 26 degrees /g, respectively, and of ocular counter-roll during roll tilts was approximately 20 degrees /g. During X-axis centripetal acceleration with 1 g of gravity along the Z-axis, pitch and vergence sensitivities were reduced to approximately 13 degrees /g and approximately 16 degrees /g. Similarly, Y-axis acceleration with 1g along the Z-axis reduced the roll sensitivity to approximately 16 degrees /g. Modulation of Z-axis centripetal acceleration caused sensitivities to drop by approximately 6 degrees /g in pitch, approximately 2 degrees /g in vergence, and approximately 5 degrees /g in roll. Thus, the constant 1g acceleration along the Z-axis reduced the sensitivity of ocular orientation to linear accelerations in the horizontal plane. Orienting responses were also modulated by varying the head Z-axis acceleration; the sensitivity of response to Z-axis acceleration was linearly related to the response to static tilt. Although the sign of the Z-axis modulation is opposite in the lateral-eyed rabbit from that in frontal-eyed species, these data provide evidence that the brain uses both the horizontal and the vertical components of acceleration from the otolith organs to determine the magnitude of ocular orientation in response to linear acceleration

Although cerebellar Purkinje cell complex spikes occur at low frequency (approximately 1/s), each complex spike is often associated with a high-frequency burst (approximately 500/s) of climbing fiber spikes. We examined the possibility that signals are present within the climbing fiber bursts. By intracellularly recording from depolarized, nonspiking Purkinje cells in anesthetized pigmented rabbits, climbing fiber burst patterns were investigated by determining the number of components in the induced compound EPSPs during spontaneous activity and during visual stimulation. For our sample of 43 cells, >70% of all EPSPs were of the compound type composed of two or three EPSPs. During spontaneous activity, the number of components in each compound EPSP was not related to the latency to the succeeding compound EPSP. Conversely, the number of components in each compound EPSP was related to its latency after the preceding compound EPSP. This latency increased from 0.62 s for one-component EPSPs to 1.69 s for compound EPSPs with four or more components. The effect of visual stimulation on the climbing fiber activity was studied in 19 floccular Purkinje cells whose low-frequency interburst climbing fiber response was modulated by movement about the vertical axis. During sinusoidal oscillation (0.1 Hz, +/-10 degrees), compound EPSPs with a larger number of components tended to be more prevalent during movement in the excitatory direction than in the inhibitory direction. Thus, climbing fibers can, in addition to modulation of their low interburst frequency, transmit signals in the form of the number of spikes within each high-frequency burst

The electrophysiological properties of rat inferior olive (IO) neurons in the dorsal cap of Kooy (DCK) and the adjacent ventrolateral outgrowth (VLO) were compared with those of IO neurons in the principal olive (PO). Whereas DCK/VLO neurons are involved in eye movement control via their climbing fiber projection to the cerebellar flocculus, PO neurons control limb and digit movements via their climbing fiber projection to the lateral cerebellar hemisphere. In vitro patch recordings from DCK/VLO neurons revealed that low threshold calcium currents, Ih currents, and subthreshold oscillations are lacking in this subset of IO neurons. The recordings of activity in DCK neurons obtained by using voltage-sensitive dye imaging showed that activity is not limited to a single neuron, but rather that clusters of DCK neurons can be active in unison. These electrophysiological results show that the DCK/VLO neurons have unique properties that set them apart from the neurons in the PO nucleus. This finding indicates that motor control, from the perspective of the olivocerebellar system, is fundamentally different for the oculomotor and the somatomotor systems