PubMed Health⌕ Search

Biomedical subjects

Dietmar Plenz

Publications and source records attributed to Dietmar Plenz.

11 recordsLinked to original sources

Direct magnetic resonance detection of neuronal electrical activity.

Present noninvasive neuroimaging methods measure neuronal activity indirectly, via either cerebrovascular changes or extracranial measurements of electrical/magnetic signals. Recent studies have shown evidence that MRI may be used to directly and noninvasively map electrical activity associated with human brain activation, but results are inconclusive. Here, we show that MRI can detect cortical electrical activity directly. We use organotypic rat-brain cultures in vitro that are spontaneously active in the absence of a cerebrovascular system. Single-voxel magnetic resonance (MR) measurements obtained at 7 T were highly correlated with multisite extracellular local field potential recordings of the same cultures before and after blockade of neuronal activity with tetrodotoxin. Similarly, for MR images obtained at 3 T, the MR signal changed solely in voxels containing the culture, thus allowing the spatial localization of the active neuronal tissue.

Animals↗

Inverted-U profile of dopamine-NMDA-mediated spontaneous avalanche recurrence in superficial layers of rat prefrontal cortex.

Prefrontal cortex (PFC) functions, such as working memory, attention selection, and memory retrieval, depend critically on dopamine and NMDA receptor activation by way of an inverted-U-shaped pharmacological profile. Although single neuron responses in the PFC have shown some aspects of this profile, a network dynamic that follows the dopamine-NMDA dependence has not been identified. We studied neuronal network activity in acute medial PFC slices of adult rats by recording local field potentials (LFPs) with microelectrode arrays. Bath application of dopamine or the dopamine D1 agonist SKF38393 [(+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride] in combination with NMDA induced spontaneous LFPs predominantly in superficial cortex layers. The LFPs at single electrodes were characterized by sharp negative peaks that were clustered in time across electrodes revealing diverse spatiotemporal patterns on the array. The pattern formation required fast GABAergic transmission, coactivation of the dopamine D1 and NMDA receptor, and depended in an inverted-U profile on dopamine. At moderate concentrations of dopamine or the dopamine D1 agonist, the pattern size distribution formed a power law with exponent alpha = -1.5, indicating that patterns are organized in the form of neuronal avalanches, thereby maximizing spatial correlations in the network. At lower or higher concentrations, alpha was more negative than -1.5, indicating reduced spatial correlations. Likewise, at moderate dopamine concentrations, the avalanche rate and recurrence of specific avalanches was maximal with recurrence frequencies after a "power law"-like heavy-tail distribution with a slope of -2.4. We suggest that the dopamine-NMDA-dependent spontaneous recurrence of specific avalanches in superficial cortical layers might facilitate integrative and associative aspects of PFC functions.

Action Potentials↗

A comparative voltage and current-clamp analysis of feedback and feedforward synaptic transmission in the striatal microcircuit in vitro.

Striatal spiny projection (SP) neurons control movement initiation by integrating cortical inputs and inhibiting basal ganglia outputs. Central to this control lies a "microcircuit" that consists of a feedback pathway formed by axon collaterals between GABAergic SP neurons and a feedforward pathway from fast spiking (FS) GABAergic interneurons to SP neurons. Here, somatically evoked postsynaptic potentials (PSPs) and currents (PSCs) were compared for both pathways with dual whole cell patch recording in voltage- and current-clamp mode using cortex-striatum-substantia nigra organotypic cultures. On average, feedforward inputs were 1 ms earlier, more reliable, and about twice as large in amplitude compared with most feedback inputs. On the other hand, both pathways exhibited widely varying, partially overlapping amplitude distributions. This variability was already established for single FS neurons targeting many SP neurons. In response to precisely timed action potential bursts, feedforward and feedback inputs consistently showed short-term depression < or =50-70% in voltage-clamp, although feedback inputs also displayed strong augmentation in current-clamp in line with previous reports. The augmentation of feedback inputs was absent in gramicidin D perforated-patch recording, which also showed the natural reversal potential for both inputs to be near firing threshold. Preceding depolarizing feedback inputs during the down state did not consistently change subsequent postsynaptic action potentials. We conclude that feedback and feedforward inputs have their dominant effect during the up-state. The reversal potential close to the up-state potential, which supports shunting operation with millisecond precision and the strong synaptic depression, should enable both pathways to carry time-critical information.

Action Potentials↗

Neuronal avalanches are diverse and precise activity patterns that are stable for many hours in cortical slice cultures.

A major goal of neuroscience is to elucidate mechanisms of cortical information processing and storage. Previous work from our laboratory (Beggs and Plenz, 2003) revealed that propagation of local field potentials (LFPs) in cortical circuits could be described by the same equations that govern avalanches. Whereas modeling studies suggested that these "neuronal avalanches" were optimal for information transmission, it was not clear what role they could play in information storage. Work from numerous other laboratories has shown that cortical structures can generate reproducible spatiotemporal patterns of activity that could be used as a substrate for memory. Here, we show that although neuronal avalanches lasted only a few milliseconds, their spatiotemporal patterns were also stable and significantly repeatable even many hours later. To investigate these issues, we cultured coronal slices of rat cortex for 4 weeks on 60-channel microelectrode arrays and recorded spontaneous extracellular LFPs continuously for 10 hr. Using correlation-based clustering and a global contrast function, we found that each cortical culture spontaneously produced 4736 +/- 2769 (mean +/- SD) neuronal avalanches per hour that clustered into 30 +/- 14 statistically significant families of spatiotemporal patterns. In 10 hr of recording, over 98% of the mutual information shared by these avalanche patterns were retained. Additionally, jittering analysis revealed that the correlations between avalanches were temporally precise to within +/-4 msec. The long-term stability, diversity, and temporal precision of these avalanches indicate that they fulfill many of the requirements expected of a substrate for memory and suggest that they play a central role in both information transmission and storage within cortical networks.

Action Potentials↗

Action potential timing determines dendritic calcium during striatal up-states.

Up-states represent a key feature of synaptic integration in cortex and striatum that involves activation of many synaptic inputs. In the striatum, the sparse firing and tight control of action potential timing is in contrast to the large intracellular membrane potential depolarizations observed during the up-state. One hallmark of striatal spiny projection neurons is the delay to action potential generation in both up-states and suprathreshold depolarization by somatic current injection. By studying somatic and dendritic intracellular calcium ([Ca2+]i) transients during spontaneous up-states in cortex-striatum-substantia nigra organotypic cultures, we show that the delay between up-state onset and action potential generation determines dendritic peak [Ca2+]i. Peak [Ca2+]i from single action potentials reached maximum values when action potentials were close to up-state onset and sharply decayed to near subthreshold up-state [Ca2+] levels as a function of time (tau = 47 +/- 26 msec for tertiary dendrite). Similarly, a precisely timed action potential elicited during subthreshold up-states through somatic current injection established that the delay between up-state onset and action potential generation is the critical variable that controls peak [Ca2+]i. Blocking NMDA channels internally with high intracellular Mg2+ ([Mg2+]i) (10 mm) abolished the dependency of peak [Ca2+]i on action potential timing during spontaneous up-states. Finally, high [Mg2+]i specifically blocked [Ca2+]i transients that resulted from local NMDA application in conjunction with backpropagating action potentials. We conclude that precisely timed, single action potentials during striatal up-states control peak dendritic calcium levels. We suggest that this mechanism might play an important role in synaptic plasticity of the corticostriatal pathway.

Action Potentials↗

Neuronal avalanches in neocortical circuits.

Networks of living neurons exhibit diverse patterns of activity, including oscillations, synchrony, and waves. Recent work in physics has shown yet another mode of activity in systems composed of many nonlinear units interacting locally. For example, avalanches, earthquakes, and forest fires all propagate in systems organized into a critical state in which event sizes show no characteristic scale and are described by power laws. We hypothesized that a similar mode of activity with complex emergent properties could exist in networks of cortical neurons. We investigated this issue in mature organotypic cultures and acute slices of rat cortex by recording spontaneous local field potentials continuously using a 60 channel multielectrode array. Here, we show that propagation of spontaneous activity in cortical networks is described by equations that govern avalanches. As predicted by theory for a critical branching process, the propagation obeys a power law with an exponent of -3/2 for event sizes, with a branching parameter close to the critical value of 1. Simulations show that a branching parameter at this value optimizes information transmission in feedforward networks, while preventing runaway network excitation. Our findings suggest that "neuronal avalanches" may be a generic property of cortical networks, and represent a mode of activity that differs profoundly from oscillatory, synchronized, or wave-like network states. In the critical state, the network may satisfy the competing demands of information transmission and network stability.

Animals↗

Quantitative estimate of synaptic inputs to striatal neurons during up and down states in vitro.

Up states are prolonged membrane potential depolarizations critical for synaptic integration and action potential generation in cortical and striatal neurons. They commonly result from numerous concurrent synaptic inputs, whereas neurons reside in a down state when synaptic inputs are few. By quantifying the composition, frequency, and amplitude of synaptic inputs for both states, we provide important constraints for state transitions in striatal network dynamics. Up and down states occur naturally in cortex-striatum-substantia nigra cocultures, which were used as an in vitro model in the present study. Spontaneous synaptic inputs during down states were extracted automatically in spiny projection neurons and fast spiking interneurons of the striatum using a newly developed computer algorithm. Consistent with a heterogeneous population of synaptic inputs, PSPs and PSCs showed no correlation in amplitude and rise time and occurred at relatively low frequencies of 10-40 Hz during the down state. The number of synaptic inputs during up states, estimated from the up-state charge and the unitary charge of down-state PSCs, was 217 +/- 44. Given the average up-state duration of 284 +/- 34 msec, synaptic input frequency was approximately 800 Hz during up-states for both neuronal types. Many down-state events reversed at the chloride reversal potential and were blocked by GABA(A) antagonists. The high correlation between up- and down-state reversal potential suggests that despite these drastic changes in synaptic input frequency, the ratio of inhibitory to excitatory currents is similar during both states.

Action Potentials↗

When inhibition goes incognito: feedback interaction between spiny projection neurons in striatal function.

Theories about basal ganglia function have always been driven by our knowledge about the spiny projection neurons of the striatum. At the core of these theories lies the question of how, precisely, spiny projection neurons process cortical inputs. Most recently, studies demonstrating the role of spiny projection neurons in local synaptic GABA transmission have provided several new avenues for exploring striatal dynamics. They have also suggested new experimental directives for examining the specific ways in which spiny projection neurons both compete and cooperate through their local axon collaterals during cortical input processing.

Animals↗

Fast synaptic transmission between striatal spiny projection neurons.

Striatal inhibition plays an important role in models of cortex-basal ganglia function and is altered in many basal ganglia diseases. The gamma-aminobutyric acid ergic spiny projection neuron comprises >95% of striatal neurons, but despite strong anatomical evidence, the electrophysiological properties and functions of their local axon collaterals are unknown. We simultaneously recorded from adjacent spiny projection neurons (<5-10 microm) in whole-cell patch mode and demonstrated a fast synaptic connection between 2669 pairs in cortex-striatum-substantia nigra organotypic cultures and 538 pairs in acute striatal slices. The synapse, which was blocked by gamma-aminobutyric acid type A antagonists, displayed a wide range of failure rates, was depolarizing at rest, and reversed above -60 mV. Presynaptic bursts of action potentials were highly correlated with total postsynaptic depolarization at rest. Synaptic transmission was optimized for burst discharge >14 Hz and showed considerable short-term plasticity, including paired-pulse depression at intervals <25 ms, intraburst facilitation, and interburst augmentation. This activity-dependent collateral interaction provides the basis for a new class of basal ganglia models in which striatal neurons cooperate as well as compete during processing of cortical inputs.

Action Potentials↗

Dendritic calcium encodes striatal neuron output during up-states.

Striatal spiny projection neurons control basal ganglia outputs via action potential bursts conveyed to the globus pallidus and substantia nigra. Accordingly, burst activity in these neurons contributes importantly to basal ganglia function and dysfunction. These bursts are driven by multiple corticostriatal inputs that depolarize spiny projection neurons from their resting potential of approximately -85 mV, which is the down-state, to a subthreshold up-state of -55 mV. To understand dendritic processing of bursts during up-states, changes in intracellular calcium concentration ([Ca2+]i) were measured in striatal spiny projection neurons from cortex-striatum-substantia nigra organotypic cultures grown for 5-6 weeks using somatic whole-cell patch recording and Fura-2. During up-states, [Ca2+]i transients at soma and primary, secondary, and tertiary dendrites were highly correlated with burst strength (i.e., the number of spontaneous action potentials). During down-states, the action potentials evoked by somatic current pulses elicited [Ca2+]i transients in higher-order dendrites that were also correlated with burst strength. Evoked bursts during up-states increased dendritic [Ca2+]i transients supralinearly by >200% compared with the down-state. In the presence of tetrodotoxin, burst-like voltage commands failed to elicit [Ca2+]i transients at higher-order dendrites. Thus, dendritic [Ca2+]i transients in spiny projection neurons encode somatic bursts supralinearly during up-states through active propagation of action potentials along dendrites. We suggest that this conveys information about the contribution of a spiny projection neuron to a basal ganglia output specifically back to the corticostriatal synapses involved in generating these outputs.

Action Potentials↗