Claudia Böhm

Inhibitory Gradient along the Dorsoventral Axis in the Medial Entorhinal Cortex

Local inhibitory microcircuits in the medial entorhinal cortex (MEC) and their role in network activity are little investigated. Using a combination of electrophysiological, optical, and morphological circuit analysis tools, we find that layer II stellate cells are embedded in a dense local inhibitory microcircuit. Specifically, we report a gradient of inhibitory inputs along the dorsoventral axis of the MEC, with the majority of this local inhibition arising from parvalbumin positive (PV+) interneurons. Finally, the gradient of PV+ fibers is accompanied by a gradient in the power of extracellular network oscillations in the gamma range, measured both in vitro and in vivo. The reported differences in the inhibitory microcircuitry in layer II of the MEC may therefore have a profound functional impact on the computational working principles at different locations of the entorhinal network and influence the input pathways to the hippocampus.

Cannabinoids disrupt hippocampal sharp wave-ripples via inhibition of glutamate release

Cannabis consumption results in impaired learning. The proper synchronization of neuronal activity in the mammalian hippocampus gives rise to network rhythms that are implicated in memory formation. Here, we have studied the impact of cannabinoids on hippocampal sharp waves and associated ripple oscillations using field‐ and whole‐cell voltage‐clamp recordings. We demonstrate that the activation of cannabinoid receptor 1 suppresses sharp wave‐ripples (SWRs) in mice in vivo and in vitro. This suppression was paralleled by a selective reduction of SWR‐associated inward but not outward charge transfer, demonstrating an impairment of excitation due to cannabinoid exposure. Adenosine, a presynaptic modulator of glutamate release, mimicked and occluded the observed consequences of cannabinoids on SWRs. We conclude that inhibition of glutamatergic feed‐forward excitation can explain cannabinoid‐mediated disruption of SWRs and may account for cannabinoid‐induced impairment of hippocampus‐dependent memory.

Functional diversity of subicular principal cells during hippocampal ripples

Cortical and hippocampal oscillations play a crucial role in the encoding, consolidation, and retrieval of memory. Sharp-wave associated ripples have been shown to be necessary for the consolidation of memory. During consolidation, information is transferred from the hippocampus to the neocortex. One of the structures at the interface between hippocampus and neocortex is the subiculum. It is therefore well suited to mediate the transfer and distribution of information from the hippocampus to other areas. By juxtacellular and whole-cell-recordings in awake mice, we show here that in the subiculum a subset of pyramidal cells is activated, whereas another subset is inhibited during ripples. We demonstrate that these functionally different subgroups are predetermined by their cell subtype. Bursting cells are selectively used to transmit information during ripples, whereas the firing probability in regular firing cells is reduced. With multiple patch-clamp recordings in vitro, we show that the cell subtype-specific differences extend into the local network topology. This is reflected in an asymmetric wiring scheme where bursting cells and regular firing cells are recurrently connected among themselves but connections between subtypes exclusively exist from regular to bursting cells. Furthermore, inhibitory connections are more numerous onto regular firing cells than onto bursting cells. We conclude that the network topology contributes to the observed functional diversity of subicular pyramidal cells during sharp-wave associated ripples. SIGNIFICANCE STATEMENT Memory consolidation is dependent on hippocampal activity patterns, so called hippocampal ripples. During these fast oscillations, memory traces are transferred from the hippocampus to the neocortex via the subiculum. We investigated the role of single cells in the subiculum during ripples and found that, dependent on their subtype, they are preferentially activated or inhibited. In addition, these two subtypes, the bursting and regular firing type, are differentially integrated into the local network: inhibitory cells are more densely connected to regular firing cells, and communication between regular and bursting cells is unidirectional. Together with earlier findings on different preferential target regions of these subtypes, we conclude that memory traces are guided to target regions of the activated cell type.

Cell-specific synaptic plasticity induced by network oscillations

Gamma rhythms are known to contribute to the process of memory encoding. However, little is known about the underlying mechanisms at the molecular, cellular and network levels. Using local field potential recording in awake behaving mice and concomitant field potential and whole-cell recordings in slice preparations we found that gamma rhythms lead to activity-dependent modification of hippocampal networks, including alterations in sharp wave-ripple complexes. Network plasticity, expressed as long-lasting increases in sharp wave-associated synaptic currents, exhibits enhanced excitatory synaptic strength in pyramidal cells that is induced postsynaptically and depends on metabotropic glutamate receptor-5 activation. In sharp contrast, alteration of inhibitory synaptic strength is independent of postsynaptic activation and less pronounced. Further, we found a cell type-specific, directionally biased synaptic plasticity of two major types of GABAergic cells, parvalbumin- and cholecystokinin-expressing interneurons. Thus, we propose that gamma frequency oscillations represent a network state that introduces long-lasting synaptic plasticity in a cell-specific manner. DOI: http://dx.doi.org/10.7554/eLife.14912.001

Serotonin Attenuates Feedback Excitation onto O-LM Interneurons

The serotonergic system is a subcortical neuromodulatory center that controls cortical information processing in a state-dependent manner. In the hippocampus, serotonin (5-HT) is released by ascending serotonergic fibers from the midbrain raphe nuclei, thereby mediating numerous modulatory functions on various neuronal subtypes. Here, we focus on the neuromodulatory effects of 5-HT on GABAergic inhibitory oriens lacunosum-moleculare (O-LM) cells in the hippocampal area CA1 of the rat. These interneurons are thought to receive primarily local excitatory input and are, via their axonal projections to stratum lacunosum-moleculare, ideally suited to control entorhinal cortex input. We show that 5-HT reduces excitatory glutamatergic transmission onto O-LM interneurons. By means of paired recordings from synaptically connected CA1 pyramidal cells and O-LM interneurons we reveal that this synapse is modulated by 5-HT. Furthermore, we demonstrate that the reduction of glutamatergic transmission by serotonin is likely to be mediated via a decrease of calcium influx into presynaptic terminals of CA1 pyramidal cells. This modulation of excitatory synaptic transmission onto O-LM interneurons by 5-HT might be a mechanism to vary the activation of O-LM interneurons during ongoing network activity and serve as a brain state-dependent switch gating the efficiency of entorhinal cortex input to CA1 pyramidal neurons.

Psychische Störung und Aussagetüchtigkeit

ZusammenfassungDer Artikel stellt die Vorgehensweise bei der psychiatrischen Beurteilung der Aussagetüchtigkeit dar und geht dabei auf einzelne Störungsbilder bzw. -gruppen ein. Anlass für psychiatrische Gutachten zur Aussagetüchtigkeit bilden häufig psychopathologische Auffälligkeiten eines Zeugen oder dessen psychiatrische (bzw. psychotherapeutische) Behandlungen. Die psychiatrische Beurteilung der Aussagetüchtigkeit erfolgt in zwei Schritten. Nur bei Vorliegen einer psychiatrischen Diagnose muss über eine Beeinträchtigung der Fähigkeiten, eine gerichtsverwertbare Aussage zu machen, diskutiert werden. Die Aufhebung der Aussagetüchtigkeit ist nur in wenigen Fällen im Rahmen klassischer psychiatrischer Erkrankungen, psychotischer Zustände oder Intoxikationen anzunehmen. Andere Diagnosen rechtfertigen dagegen in der Regel nicht die Annahme, ein Zeuge sei aussageuntüchtig.SummaryThe article describes the approach used in the psychiatric assessment of a person’s competence to testify and discusses different disorders. Psychiatrists are often asked to comment on the competence to give evidence if witnesses’ behaviour suggests psychopathology or they are undergoing psychiatric treatment or psychotherapy. Competence to testify is assessed in two steps. Impaired capacity to give evidence does not necessarily have to be considered unless a psychiatric diagnosis has been made. It is very rare for a witness to be declared incompetent to testify; incompetence is assumed only in the context of classic psychiatric illnesses, psychotic states or intoxications. Other diagnoses generally do not justify the assumption of incompetence to testify.

Routes to, from and within the subiculum

The subiculum is one of the major output areas of the hippocampus and has extensive projections to extrahippocampal targets. It is likely to play a pivotal role in the distribution of outgoing information from the hippocampus. The hippocampus, including the subiculum, is important for the formation, consolidation and retrieval of memory. These functions require a network that is flexible enough to encode incoming information and also allows for reliable distribution, storage and integration into previously encoded memories. Finally, relevant information has to be retrieved in a context-specific manner to allow for an appropriate behavioral response. The subiculum as a gateway between the hippocampus and cortex might serve to integrate and process information from the hippocampus proper and its other inputs before conveying it to more permanent storage locations. This review summarizes how the subiculum is embedded into upstream and downstream circuits, describes what is known about the local network topology and discusses cellular and functional properties of subicular cells subtypes. Lastly, it describes how these properties might help to separate information into parallel output streams and distribute it to its multiple target areas.

Mental disorder and competence to testify

ZusammenfassungDer Artikel stellt die Vorgehensweise bei der psychiatrischen Beurteilung der Aussagetüchtigkeit dar und geht dabei auf einzelne Störungsbilder bzw. -gruppen ein. Anlass für psychiatrische Gutachten zur Aussagetüchtigkeit bilden häufig psychopathologische Auffälligkeiten eines Zeugen oder dessen psychiatrische (bzw. psychotherapeutische) Behandlungen. Die psychiatrische Beurteilung der Aussagetüchtigkeit erfolgt in zwei Schritten. Nur bei Vorliegen einer psychiatrischen Diagnose muss über eine Beeinträchtigung der Fähigkeiten, eine gerichtsverwertbare Aussage zu machen, diskutiert werden. Die Aufhebung der Aussagetüchtigkeit ist nur in wenigen Fällen im Rahmen klassischer psychiatrischer Erkrankungen, psychotischer Zustände oder Intoxikationen anzunehmen. Andere Diagnosen rechtfertigen dagegen in der Regel nicht die Annahme, ein Zeuge sei aussageuntüchtig.SummaryThe article describes the approach used in the psychiatric assessment of a person’s competence to testify and discusses different disorders. Psychiatrists are often asked to comment on the competence to give evidence if witnesses’ behaviour suggests psychopathology or they are undergoing psychiatric treatment or psychotherapy. Competence to testify is assessed in two steps. Impaired capacity to give evidence does not necessarily have to be considered unless a psychiatric diagnosis has been made. It is very rare for a witness to be declared incompetent to testify; incompetence is assumed only in the context of classic psychiatric illnesses, psychotic states or intoxications. Other diagnoses generally do not justify the assumption of incompetence to testify.

Psychische Störung und Aussagetüchtigkeit@@@Mental disorder and competence to testify

ZusammenfassungDer Artikel stellt die Vorgehensweise bei der psychiatrischen Beurteilung der Aussagetüchtigkeit dar und geht dabei auf einzelne Störungsbilder bzw. -gruppen ein. Anlass für psychiatrische Gutachten zur Aussagetüchtigkeit bilden häufig psychopathologische Auffälligkeiten eines Zeugen oder dessen psychiatrische (bzw. psychotherapeutische) Behandlungen. Die psychiatrische Beurteilung der Aussagetüchtigkeit erfolgt in zwei Schritten. Nur bei Vorliegen einer psychiatrischen Diagnose muss über eine Beeinträchtigung der Fähigkeiten, eine gerichtsverwertbare Aussage zu machen, diskutiert werden. Die Aufhebung der Aussagetüchtigkeit ist nur in wenigen Fällen im Rahmen klassischer psychiatrischer Erkrankungen, psychotischer Zustände oder Intoxikationen anzunehmen. Andere Diagnosen rechtfertigen dagegen in der Regel nicht die Annahme, ein Zeuge sei aussageuntüchtig.SummaryThe article describes the approach used in the psychiatric assessment of a person’s competence to testify and discusses different disorders. Psychiatrists are often asked to comment on the competence to give evidence if witnesses’ behaviour suggests psychopathology or they are undergoing psychiatric treatment or psychotherapy. Competence to testify is assessed in two steps. Impaired capacity to give evidence does not necessarily have to be considered unless a psychiatric diagnosis has been made. It is very rare for a witness to be declared incompetent to testify; incompetence is assumed only in the context of classic psychiatric illnesses, psychotic states or intoxications. Other diagnoses generally do not justify the assumption of incompetence to testify.