Like a clock in the rabbit's visual cortex.

Three rules govern the connectivity between neurons in the thalamus and inhibitory neurons in the visual cortex of rabbits.

Thalamocortical synapses in the cat visual system in vivo are weak and unreliable.

The thalamocortical synapse of the visual system has been central to our understanding of sensory computations in the cortex. Although we have a fair understanding of the functional properties of the pre and post-synaptic populations, little is known about their synaptic properties, particularly in vivo. We used simultaneous recordings in LGN and V1 in cat in vivo to characterize the dynamic properties of thalamocortical synaptic transmission in monosynaptically connected LGN-V1 neurons. We found that thalamocortical synapses in vivo are unreliable, highly variable and exhibit short-term plasticity. Using biologically constrained models, we found that variable and unreliable synapses serve to increase cortical firing by means of increasing membrane fluctuations, similar to high conductance states. Thus, synaptic variability and unreliability, rather than acting as system noise, do serve a computational function. Our characterization of LGN-V1 synaptic properties constrains existing mathematical models, and mechanistic hypotheses, of a fundamental circuit in computational neuroscience.

Intracellular, In Vivo, Dynamics of Thalamocortical Synapses in Visual Cortex.

Seminal studies of the thalamocortical circuit in the visual system of the cat have been central to our understanding of sensory encoding. However, thalamocortical synaptic properties remain poorly understood. We used paired recordings, in the lateral geniculate nucleus (LGN) and primary visual cortex (V1), to provide the first in vivo characterization of sensory-driven thalamocortical potentials in V1. The amplitudes of EPSPs we characterized were smaller than those previously reported in vitro Consistent with prior findings, connected LGN-V1 pairs were only found when their receptive fields (RFs) overlapped, and the probability of connection increased steeply with degree of RF overlap and response similarity. However, surprisingly, we found no relationship between EPSP amplitudes and the similarity of RFs or responses, suggesting different connectivity models for intracortical and thalamocortical circuits. Putative excitatory regular-spiking (RS) and inhibitory fast-spiking (FS) V1 cells had similar EPSP characteristics, showing that in the visual system, feedforward excitation and inhibition are driven with equal strength by the thalamus. Similar to observations in the somatosensory cortex, FS V1 cells received less specific input from LGN. Finally, orientation tuning in V1 was not inherited from single presynaptic LGN cells, suggesting that it must emerge exclusively from the combined input of all presynaptic LGN cells. Our results help to decipher early visual encoding circuits and have immediate utility in providing physiological constraints to computational models of the visual system.SIGNIFICANCE STATEMENT To understand how the brain encodes the visual environment, we must understand the transfer of visual signals between various regions of the brain. Therefore, understanding synaptic dynamics is critical to our understanding of sensory encoding. This study provides the first characterization of visually evoked synaptic potentials between the visual thalamus and visual cortex in an intact animal. To record these potentials, we simultaneously recorded the extracellular potential of presynaptic thalamic cells and the intracellular potential of postsynaptic cortical cells in input layers of primary visual cortex. Our characterization of synaptic potentials in vivo disagreed with prior findings in vitro This study will increase our understanding of thalamocortical circuits and will improve computational models of visual encoding.

Disruption of polycystin-L causes hippocampal and thalamocortical hyperexcitability.

Epilepsy or seizure disorder is among the least understood chronic medical conditions affecting over 65 million people worldwide. Here, we show that disruption of the polycystic kidney disease 2-like 1 (Pkd2l1 or Pkdl), encoding polycystin-L (PCL), a non-selective cation channel, increases neuronal excitability and the susceptibility to pentylenetetrazol-induced seizure in mice. PCL interacts with ß2-adrenergic receptor (ß2AR) and co-localizes with ß2AR on the primary cilia of neurons in the brain. Pkdl deficiency leads to the loss of ß2AR on neuronal cilia, which is accompanied with a remarkable reduction in cAMP levels in the central nervous system (CNS). The reduction of cAMP levels is associated with a reduction in the activation of cAMP response element-binding protein, but not the activation of Ca(2+)/calmodulin-dependent protein kinase II, Akt or mitogen-activated protein kinases. Our data, thus, indicate for the first time that a ciliary protein complex is required for the control of neuronal excitability in the CNS.

[Opinions of medical students about complementary therapies]. / Opiniones sobre terapias complementarias por parte de los estudiantes de medicina de la Pontificia Universidad Católica de Chile. Año 2014.

BACKGROUND: There is increasing national and worldwide interest on complementary therapies (CT). AIM: To describe and analyze the opinions and interest about CT among medical students. MATERIAL AND METHODS: An anonymous and voluntary survey with questions used in previous studies, was applied to students from first to fifth year. RESULTS: The survey was answered by 526 medical students, corresponding to 86% of the target population. The students knew about an average of 4.7 therapies, out of 12 displayed. The better known therapy was acupuncture, followed by homeopathy and reiki, which raised the greater interest. The knowledge and interest was higher among women, who also had a more favorable opinion about CT. The interest decreases and the proportion of unfavorable opinions increases among students of upper level courses. Forty nine percent of respondents have used CT for themselves and 22% had no experience whatsoever with them. CONCLUSIONS: In general, there is an appreciable knowledge, experience, interest and positive opinions toward CT. This favorable attitude is higher in women and decreases as career progresses. Medical students consider that they should have some approach to CT during their career.

Opiniones sobre terapias complementarias por parte de los estudiantes de medicina de la Pontificia Universidad Católica de Chile. Año 2014 / Opinions of medical students about complementary therapies

Background: There is increasing national and worldwide interest on complementary therapies (CT). Aim: To describe and analyze the opinions and interest about CT among medical students. Material and Methods: An anonymous and voluntary survey with questions used in previous studies, was applied to students from first to fifth year. Results: The survey was answered by 526 medical students, corresponding to 86% of the target population. The students knew about an average of 4.7 therapies, out of 12 displayed. The better known therapy was acupuncture, followed by homeopathy and reiki, which raised the greater interest. The knowledge and interest was higher among women, who also had a more favorable opinion about CT. The interest decreases and the proportion of unfavorable opinions increases among students of upper level courses. Forty nine percent of respondents have used CT for themselves and 22% had no experience whatsoever with them. Conclusions: In general, there is an appreciable knowledge, experience, interest and positive opinions toward CT. This favorable attitude is higher in women and decreases as career progresses. Medical students consider that they should have some approach to CT during their career.

Differential modulation of spontaneous and evoked thalamocortical network activity by acetylcholine level in vitro.

Different levels of cholinergic neuromodulatory tone have been hypothesized to set the state of cortical circuits either to one dominated by local cortical recurrent activity (low ACh) or to one dependent on thalamic input (high ACh). High ACh levels depress intracortical but facilitate thalamocortical synapses, whereas low levels potentiate intracortical synapses. Furthermore, recent work has implicated the thalamus in controlling cortical network state during waking and attention, when ACh levels are highest. To test this hypothesis, we used rat thalamocortical slices maintained in medium to generate spontaneous up- and down-states and applied different ACh concentrations to slices in which thalamocortical connections were either maintained or severed. The effects on spontaneous and evoked up-states were measured using voltage-sensitive dye imaging, intracellular recordings, local field potentials, and single/multiunit activity. We found that high ACh can increase the frequency of spontaneous up-states, but reduces their duration in slices with intact thalamocortical connections. Strikingly, when thalamic connections are severed, high ACh instead greatly reduces or abolishes spontaneous up-states. Furthermore, high ACh reduces the spatial propagation, velocity, and depolarization amplitude of evoked up-states. In contrast, low ACh dramatically increases up-state frequency regardless of the presence or absence of intact thalamocortical connections and does not reduce the duration, spatial propagation, or velocity of evoked up-states. Therefore, our data support the hypothesis that strong cholinergic modulation increases the influence, and thus the signal-to-noise ratio, of afferent input over local cortical activity and that lower cholinergic tone enhances recurrent cortical activity regardless of thalamic input.

Columnar interactions determine horizontal propagation of recurrent network activity in neocortex.

The cortex is organized in vertical and horizontal circuits that determine the spatiotemporal properties of distributed cortical activity. Despite detailed knowledge of synaptic interactions among individual cells in the neocortex, little is known about the rules governing interactions among local populations. Here, we used self-sustained recurrent activity generated in cortex, also known as up-states, in rat thalamocortical slices in vitro to understand interactions among laminar and horizontal circuits. By means of intracellular recordings and fast optical imaging with voltage-sensitive dyes, we show that single thalamic inputs activate the cortical column in a preferential layer 4 (L4) → layer 2/3 (L2/3) → layer 5 (L5) sequence, followed by horizontal propagation with a leading front in supragranular and infragranular layers. To understand the laminar and columnar interactions, we used focal injections of TTX to block activity in small local populations, while preserving functional connectivity in the rest of the network. We show that L2/3 alone, without underlying L5, does not generate self-sustained activity and is inefficient propagating activity horizontally. In contrast, L5 sustains activity in the absence of L2/3 and is necessary and sufficient to propagate activity horizontally. However, loss of L2/3 delays horizontal propagation via L5. Finally, L5 amplifies activity in L2/3. Our results show for the first time that columnar interactions between supragranular and infragranular layers are required for the normal propagation of activity in the neocortex. Our data suggest that supragranular and infragranular circuits, with their specific and complex set of inputs and outputs, work in tandem to determine the patterns of cortical activation observed in vivo.

Comprehensive mapping of whisker-evoked responses reveals broad, sharply tuned thalamocortical input to layer 4 of barrel cortex.

Cortical neurons are organized in columns, distinguishable by their physiological properties and input-output organization. Columns are thought to be the fundamental information-processing modules of the cortex. The barrel cortex of rats and mice is an attractive model system for the study of cortical columns, because each column is defined by a layer 4 (L4) structure called a barrel, which can be clearly visualized. A great deal of information has been collected regarding the connectivity of neurons in barrel cortex, but the nature of the input to a given L4 barrel remains unclear. We measured this input by making comprehensive maps of whisker-evoked activity in L4 of rat barrel cortex using recordings of multiunit activity and current source density analysis of local field potential recordings of animals under light isoflurane anesthesia. We found that a large number of whiskers evoked a detectable response in each barrel (mean of 13 suprathreshold, 18 subthreshold) even after cortical activity was abolished by application of muscimol, a GABA(A) agonist. We confirmed these findings with intracellular recordings and single-unit extracellular recordings in vivo. This constitutes the first direct confirmation of the hypothesis that subcortical mechanisms mediate a substantial multiwhisker input to a given cortical barrel.

The role of T-channels in the generation of thalamocortical rhythms.

The presence of T-channels in thalamic cells allows for the generation of rhythmic bursts of spikes and the existence of two firing modes in thalamic cells: tonic and bursting. This intrinsic electrophysiological property has fundamental consequences for the functional properties of the thalamus across waking and sleep stages and is centrally implicated in a growing number of pathological states. Rhythmic bursting brings about highly synchronized activity throughout corticothalamic circuits which is incompatible with the relay of information through the thalamus. Understanding the conditions that determine the change in firing mode of thalamic cells as well as the role of bursting in the generation of synchronized oscillations is critical to understand the function of the thalamus. The functional properties of T-channels and the resulting low threshold spike are discussed here with emphasis on the differences in the bursting properties of reticular thalamic and thalamocortical neurons. The role of thalamic bursting in the generation of sleep oscillations and their specific sequence during slow wave sleep will also be discussed.

Single-column thalamocortical network model exhibiting gamma oscillations, sleep spindles, and epileptogenic bursts.

To better understand population phenomena in thalamocortical neuronal ensembles, we have constructed a preliminary network model with 3,560 multicompartment neurons (containing soma, branching dendrites, and a portion of axon). Types of neurons included superficial pyramids (with regular spiking [RS] and fast rhythmic bursting [FRB] firing behaviors); RS spiny stellates; fast spiking (FS) interneurons, with basket-type and axoaxonic types of connectivity, and located in superficial and deep cortical layers; low threshold spiking (LTS) interneurons, which contacted principal cell dendrites; deep pyramids, which could have RS or intrinsic bursting (IB) firing behaviors, and endowed either with nontufted apical dendrites or with long tufted apical dendrites; thalamocortical relay (TCR) cells; and nucleus reticularis (nRT) cells. To the extent possible, both electrophysiology and synaptic connectivity were based on published data, although many arbitrary choices were necessary. In addition to synaptic connectivity (by AMPA/kainate, NMDA, and GABA(A) receptors), we also included electrical coupling between dendrites of interneurons, nRT cells, and TCR cells, and--in various combinations--electrical coupling between the proximal axons of certain cortical principal neurons. Our network model replicates several observed population phenomena, including 1) persistent gamma oscillations; 2) thalamocortical sleep spindles; 3) series of synchronized population bursts, resembling electrographic seizures; 4) isolated double population bursts with superimposed very fast oscillations (>100 Hz, "VFO"); 5) spike-wave, polyspike-wave, and fast runs (about 10 Hz). We show that epileptiform bursts, including double and multiple bursts, containing VFO occur in rat auditory cortex in vitro, in the presence of kainate, when both GABA(A) and GABA(B) receptors are blocked. Electrical coupling between axons appears necessary (as reported previously) for persistent gamma and additionally plays a role in the detailed shaping of epileptogenic events. The degree of recurrent synaptic excitation between spiny stellate cells, and their tendency to fire throughout multiple bursts, also appears critical in shaping epileptogenic events.

Nonlinear integration of sensory responses in the rat barrel cortex: an intracellular study in vivo.

To study integration of converging sensory inputs on single cortical neurons, we performed intracellular recordings in vivo in the barrel cortex of the barbiturate-anesthetized rat. We deflected the principal whisker (PW) for each cell either alone or preceded (at 20, 50, and 100 msec) by the deflection of a small number of remote whiskers (RWs) far from the PW. The synaptic responses to both the PW and the RW were similar qualitatively and consisted of excitation followed by inhibition that comprised an early and a late component. The RW response was of smaller amplitude and more often subthreshold for action potential generation. The main effect of the RW deflection was a suppression of the subsequent response to the PW that was most pronounced at the 20 msec interval and decreased progressively at the 50 and 100 msec intervals. Suppression of the spike output of the cell was not caused by hyperpolarization (subtractive inhibition) but by a reduction in the EPSP amplitude (divisive inhibition), resulting in a highly sublinear summation of the two responses. The small decrease in input resistance caused by the RW responses is not consistent with synaptic shunting as the main cause of the reduction of the EPSP amplitude. Instead, our results suggest that suppression results from a decrease in the amount of synaptic input triggered by the PW, particularly the early excitation. We suggest that this process involves a reduction in reverberant granular cell excitation that is induced by PW deflection.