Bochum, Univ., Diss., 2005. / Computerdatei im Fernzugriff.

No description available.

München, Techn. Univ., Diss., 2010.

The hippocampus contains more than 21 types of inhibitory interneurons that express different proteins and innervate different sub-domains of pyramidal cells to regulate the spatiotemporal integration of excitatory postsynaptic potentials (EPSPs) and to define temporal windows for spiking. Neurogliaform cells (NGFCs), form synapses on the distal tufts of pyramidal cell apical dendrites alongside excitatory inputs from the entorhinal cortex. NGFCs express neuronal nitric oxide synthase (nNOS), are often synaptically coupled, and fire rhythmically during theta oscillations in vivo. In this thesis, I describe a novel form of synaptic communication between these interneuron types, hereafter referred to as the firing induced suppression of inhibition (FSI). Specifically, I found that when a theta-associated activity patterns were evoked in NGFCs from rodent hippocampal slices, the cells exhibited a transient reduction in unitary IPSP amplitude. My data suggest that FSI requires the backpropagation of action potentials, calcium influx through L-type calcium channels, nNOS activity within the dendrites of interneurons, and the activation of NO-sensitive guanylyl cyclase (NOsGC) receptors that are present on presynaptic terminals. My results also demonstrate the physiological impact of this phenomenon by showing that when FSI occurs, the strength of incoming excitatory postsynaptic potentials onto NGFCs are transiently sharpened. Specifically, FSI indirectly increased the amplitude of EPSPs. Thus FSI may enhance spatial and temporal summation of excitatory inputs to NGFCs and regulate their inhibition of pyramidal cells.

Göttingen, Univ., Diss., 2004.

Maturation of motor control, including movements that can be autonomously generated by spinal circuits, relies on the development of key inputs to spinal circuitry. In particular, the development of supraspinal, sensory and motor fibers come together to form organized spinal circuits capable of producing skilled movements that are volitionally controlled. Primitive reflexes such as the palmar grasp reflex (PGR) are known to disappear during development; presumably giving way to more volitional control of hand grasping. However, the underlying changes to the spinal circuitry responsible for this transition remain to be determined. dI3 INs, a class of dorsal spinal interneurons, have positioned themselves as key mediators of reflexive grasping in early development and grasping in adult mice. The first aim of the study focused on determining the developmental time point at which the PGR disappeared. Our studies demonstrated that the PGR was lost by the third week of development. The second aim of this study focused on identifying changes in sensory innervation, presynaptic inhibition and supraspinal excitation to dI3 INs that might account for the loss of this reflex. Our studies demonstrated that while sensory innervation remained constant during development, presynaptic inhibitory terminals onto sensory afferents were found to increase during development. In addition, we report that dI3 INs receive decreasing corticospinal (CST) input during development. While these developmental changes do not fully account for the disappearance of the PGR, they provide valuable insights into how a reflex centered on a particular population develops.

Theta activity is one of the most prominent rhythms in the brain and appears to be conserved among mammals.  These 4-12 Hz oscillations have been predominantly studied in the dorsal hippocampus where they are correlated with a broad range of voluntary and exploratory behaviors. Theta activity has been also implicated in a number of mnemonic processes, long-term potentiation (LTP) induction and even acting as a global synchronizing mechanism. Moving along the dorso-ventral axis theta activity is reduced in power and desynchronized from the dorsal part. However, theta activity can also be generated in the ventral hippocampus itself during anxiety- and fear-related behaviors. Until now it was unknown which hippocampal cell population was capable to generate theta activity and it was controversial if its origin was local, in the hippocampus, or driven by other brain regions. In this thesis I present compelling in vitro and in vivo  evidence that   a subpopulation of OLM interneurons (defined by the Chrna2-cre line)  distinctively enriched  in the CA1 region of  the ventral hippocampus is implicated in LTP function (paper I,II), information control (paper V) and the induction of theta activity that is under cholinergic  control (paper IV). Importantly, a concomitant effect of the optogenetically induced theta activity is reduction in anxiety (Paper IV). Another innovation of this work was the development of a methodological approach to avoid artefactual signals when combining electrophysiology with light activation during optogenetic experiments (Paper III). In summary, the work presented in this thesis elucidates the role of a morphologically and electrophysiologially identified cell population, OLMα2 interneurons, first on the cellular, then on the circuit and ultimately on the behavioral level.

Bochum, Univ., Diss., 2005.

No description available.

The visual system is one of the most widely used and best understood sensory systems and the dorsal lateral geniculate nucleus (dLGN) of the mouse has emerged as a model for investigating the cellular and molecular mechanisms underlying the development and activity-dependent refinement of sensory connections. Thalamic organization is highly conserved throughout species and the dLGN of the mouse possesses many features common to higher mammals, such as carnivores and primates. Two general classes of neuron are present within the dLGN, thalamocortical relay cells and interneurons, both of which receive direct retinal input. Axons of relay cells exit dLGN and convey visual information to layer IV of cortex, whereas interneurons are involved in local circuitry. In addition, dLGN receives rich nonretinal input from numerous areas of the brain. Studies thus far have focused on the retinogeniculate pathway and the development of connections between retinal ganglion cells (RGCs) and relay cells has been well characterized. However, there are still a number of unanswered questions about circuit development in dLGN. Here we examined two aspects that are not well understood, the pattern of retinal convergence onto interneurons and the structural and functional innervation of nonretinal projections. To address the first issue we conducted in vitro whole-cell recordings from acute thalamic slices of GAD67-GFP mice, a transgenic strain in which dLGN interneurons express GFP. We also did 3-D reconstructions of biocytin-labeled interneurons using multi-photon laser scanning microscopy in conjunction with anterograde labeling of retinogeniculate projections to examine the distribution of retinal contacts. To begin to examine the development of nonretinal connections in dLGN we made use of a transgenic mouse (golli-τ-GFP) to visualize corticogeniculate projections, one of the largest sources of nonretinal input to dLGN. Using this mouse we studied the timing and patterning of corticogeniculate innervation in relation to the development of the retinogeniculate pathway. We also used binocular enucleation and genetic deafferentation to test whether the retina plays a role in regulating nonretinal innervation. We found that there is a coordination of retinal and nonretinal innervation in dLGN. Projections from the retina were the first to innervate and they entered dLGN at perinatal ages. They also made functional connections with both relay cells and interneurons at early postnatal ages. Interestingly, relay cells underwent a period of retinogeniculate refinement, whereas the degree of retinal convergence onto interneurons was maintained. This possibly reflects the different roles that these two cell types have in dLGN. Both structural and functional corticogeniculate innervation was delayed in comparison and occurred postnatally, however in the absence of retinal input the timing of corticogeniculate innervation was accelerated. RGCs transmit the visual information encoded in the retina to dLGN so it may be necessary for these connections to be formed before those from nonretinal projections, which serve to modulate that signal on its way to cortex. Thus precise timing of retinal and nonretinal innervation may be important for the appropriate formation of connections in the visual system and the retina seems to be playing an important role in regulating this timing.