Biomedical subjects

Detlef Heck

Publications and source records attributed to Detlef Heck.

7 recordsLinked to original sources

PubMed2005

Controlling synaptic input patterns in vitro by dynamic photo stimulation.

Recent experimental and theoretical work indicates that both the intensity and the temporal structure of synaptic activity strongly modulate the integrative properties of single neurons in the intact brain. However, studying these effects experimentally is complicated by the fact that, in experimental systems, network activity is either absent, as in the acute slice preparation, or difficult to monitor and to control, as in in vivo recordings. Here, we present a new implementation of neurotransmitter uncaging in acute brain slices that uses functional projections to generate tightly controlled, spatio-temporally structured synaptic input patterns in individual neurons. For that, a set of presynaptic neurons is activated in a precisely timed sequence through focal photolytic release of caged glutamate with the help of a fast laser scanning system. Integration of synaptic inputs can be studied in postsynaptic neurons that are not directly stimulated with the laser, but receive input from the targeted neurons through intact axonal projections. Our new approach of dynamic photo stimulation employs functional synapses, accounts for their spatial distribution on the dendrites, and thus allows study of the integrative properties of single neurons with physiologically realistic input. Data obtained with our new technique suggest that, not only the neuronal spike generator, but also synaptic transmission and dendritic integration in neocortical pyramidal cells, can be highly reliable.

Action Potentials↗

PubMed2004

Synaptic integration in rat frontal cortex shaped by network activity.

Neocortical neurons in vivo are embedded in networks with intensive ongoing activity. How this network activity affects the neurons' integrative properties and what function this may imply at the network level remain largely unknown. Most of our knowledge regarding synaptic communication and integration is based on recordings in vitro, where network activity is strongly diminished or even absent. Here, we present results from two complementary series of experiments based on intracellular in vivo recordings in anesthetized rat frontal cortex. Specifically, we measured 1) the relationship between the excursions of a neuron's membrane potential and the spiking activity in the surrounding network and 2) how the summation of several inputs to a single neuron changes with the different levels of its membrane potential excursions and the associated states of network activity. The combination of these measurements enables us to assess how the level of network activity influences synaptic integration. We present direct evidence that integration of synaptic inputs in frontal cortex is linear, independent of the level of network activity. However, during periods of high network activity, the neurons' response to synaptic input is markedly reduced in both amplitude and duration. This results in a drastic shortening of its window for temporal integration, requiring more precise coordination of presynaptic spike discharges to reliably drive the neuron to spike under conditions of high network activity. We conclude that ongoing activity, as present in the active brain, emphasizes the need for neuronal cooperation at the network level, and cannot be ignored in the exploration of cortical function.

Action Potentials↗

PubMed2003

Passive spatial and temporal integration of excitatory synaptic inputs in cerebellar Purkinje cells of young rats.

We have investigated the integration of excitatory (parallel fiber) synaptic inputs in cerebellar Purkinje cells of young rats in vitro and in a compartmental model of such a cell, based on 3D morphological reconstruction. Excitatory synaptic inputs at two independent dendritic sites were activated by electrical stimulation with various delays between the two stimuli. Population postsynaptic potentials summed linearly under current clamp condition when the two dendritic input sites were spatially separated (>200 microm) but sublinearly, in a delay dependent manner, when the input sites were close (<50 microm) to each other. Population postsynaptic currents measured under voltage clamp conditions summed linearly independent of the spatial and temporal separation of inputs. Summation of inputs in a passive compartmental model of a Purkinje cell was similar to that of Purkinje cells in vitro. We show that sublinear summation of neighboring inputs is independent of inhibitory mechanisms and suggest that sublinearity is mainly due to a locally reduced driving force.

Age Factors↗

PubMed2003

Single-unit analysis of substantia nigra pars reticulata neurons in freely behaving rats with genetic absence epilepsy.

PURPOSE: The substantia nigra pars reticulata (SNpr) is assumed to be involved in the control of several kinds of epileptic seizures, an assumption based mostly on neuropharmacologic evidence. However, only very few neurophysiological recordings from the basal ganglia support neuropharmacologic data. We investigated the electrophysiologic activity of SNpr neurons in rats with genetic absence epilepsy. METHODS: Electrocorticography (ECoG) and multi-unit recordings using permanently implanted tetrodes were obtained in freely behaving rats. After spike sorting, auto- and cross-correlation analysis was used to detect oscillatory neuronal activities and synchronizations. RESULTS: During interictal periods, neither oscillation nor synchronization could be observed in the firing patterns of SNpr neurons. At the beginning of the absence seizure, the firing rate increased significantly. The SNpr neurons started firing in bursts of action potentials. Bursts were highly correlated to the spike-and-wave discharges (SWDs) in the ECoG, mainly after the spike component of the cortical spike-and-wave complex. Moreover, pairs of SNpr neurons tended to fire synchronously. Before the end of the seizure, the firing rate decreased progressively, and the burst-firing pattern ended at or before the end of the SWDs. Once the SWDs had stopped, the SNpr neurons resumed their basal firing pattern as before the seizure onset. CONCLUSIONS: These results provide electrophysiologic evidence that firing patterns and synchronization of SNpr neurons are in phase with the occurrence of SWDs. The findings support the concept that nigral control mechanisms are involved in modulating the propagation of an ongoing generalized seizure.

Animals↗

PubMed2002

Cerebellar structure and function: making sense of parallel fibers.

Many parts of the brain have to cooperate in a finely tuned way in order to generate coordinated motor output. Parameters of these cooperations are adjusted during early childhood development and years of motor learning later in life. The cerebellum plays a special role in the concert of these brain structures. With the unusual geometrical arrangement of its neuronal elements, especially of parallel fibers and Purkinje cells the cerebellum is a selective and sensitive detector of a specific class of spatio-temporal activity patterns in the mossy fiber system: sequences of excitatory input which 'move' along the direction of parallel fibers at about 0.5 m/s, i.e. the speed of spike conductance in parallel fibers. Precise spatio-temporal neuronal activity patterns have been shown to occur in two major sources of afference to the cerebellum, the neocortex and the sensory feedback system. Based on our own experimental work and the above-mentioned findings we suggest that the cerebellum detects specific spatio-temporal activity patterns which trigger learned cerebellar output related to motor control and which contributes to the control of precise timing of muscle contraction.

Adult↗

PubMed2002

Dynamic correlation of neuronal activity in rat cerebellar cortex modulated by behavior.

Sprague-Dawley rats (2-4 months old) were trained to perform a reaching-grasping task while their head was fixated and multielectrode recordings were performed in the ipsilateral cerebellar hemisphere. Multiunit (MU) activity was recorded with 2-3 electrodes in the Purkinje cell layer at various depths (1.5-4.5 mm) from the pial surface while the animal either performed the reaching-grasping task or was at rest. Recording sites were visually aligned along the transverse or the sagittal axis of Crus IIa. Excess correlations of MU spike activity were calculated at 10-ms time resolution using the joint peristimulus time histogram (JPSTH), to reveal the dynamics of cross-correlations corrected for nonstationarities in spike rates. Peak correlation amplitudes and areas were calculated separately for a time period preceding the movement and for a succeeding period during which the movement occurred. Correlations were compared across different paradigms: transversal versus sagittal alignment of recordings sites and behavior versus rest. No significant differences were found between transversally and sagittally aligned recording sites. Significant differences in peak correlation amplitude and/or peak area, however, were found both between premovement and movement time, as well as between both these time periods and periods while the animal was at rest.

Action Potentials↗

PubMedDate not supplied

Detection of sequences in the cerebellar cortex: numerical estimate of the possible number of tidal-wave inducing sequences represented.

The two major cortices of the brain--the cerebral and cerebellar cortex--are massively connected through intercalated nuclei (pontine, cerebellar and thalamic nuclei). We suggest that the two cortices co-operate by generating precise temporal patterns in the cerebral cortex that are detected in the cerebellar cortex as temporal patterns assembled spatially in the mossy fibers. We will begin by showing that the tidal-wave mechanism works in the cerebellar cortex as a read-out mechanism for such spatio-temporal patterns due to the synchronous activity they generate in the parallel fiber system which drives the Purkinje cells--the output neurons of the cerebellar cortex--to fire action potentials. We will review the anatomy of the mossy fibers and show that within a "beam", or "row" of cerebellar cortex the mossy fibers in principle could embed a vast number of tidal-wave generating sequences. Based on anatomical data we will argue that the cerebellar mossy fiber-granule cell-Purkinje cell system can potentially detect and--through learning--select from an enormous number of spatio-temporal patterns.

Animals↗