Hippocampal theta oscillations support encoding of an animal's position during spatial navigation, yet longstanding questions about their impact on locomotion remain unanswered. Combining optogenetic control of hippocampal theta oscillations with electrophysiological recordings in mice, we show that hippocampal theta oscillations regulate locomotion. In particular, we demonstrate that their regularity underlies more stable and slower running speeds during exploration. More regular theta oscillations are accompanied by more regular theta-rhythmic spiking output of pyramidal cells. Theta oscillations are coordinated between the hippocampus and its main subcortical output, the lateral septum (LS). Chemo- or optogenetic inhibition of this pathway reveals its necessity for the hippocampal regulation of running speed. Moreover, theta-rhythmic stimulation of LS projections to the lateral hypothalamus replicates the reduction of running speed induced by more regular hippocampal theta oscillations. These results suggest that changes in hippocampal theta synchronization are translated into rapid adjustment of running speed via the LS.

Both humans and animals seek primary rewards in the environment, even when such rewards do not correspond to current physiological needs. An example of this is a dissociation between food-seeking behaviour and metabolic needs, a notoriously difficult-to-treat symptom of eating disorders. Feeding relies on distinct cell groups in the hypothalamus, the activity of which also changes in anticipation of feeding onset. The hypothalamus receives strong descending inputs from the lateral septum, which is connected, in turn, with cortical networks, but cognitive regulation of feeding-related behaviours is not yet understood. Cortical cognitive processing involves gamma oscillations, which support memory, attention, cognitive flexibility and sensory responses. These functions contribute crucially to feeding behaviour by unknown neural mechanisms. Here we show that coordinated gamma (30-90 Hz) oscillations in the lateral hypothalamus and upstream brain regions organize food-seeking behaviour in mice. Gamma-rhythmic input to the lateral hypothalamus from somatostatin-positive lateral septum cells evokes food approach without affecting food intake. Inhibitory inputs from the lateral septum enable separate signalling by lateral hypothalamus neurons according to their feeding-related activity, making them fire at distinct phases of the gamma oscillation. Upstream, medial prefrontal cortical projections provide gamma-rhythmic inputs to the lateral septum; these inputs are causally associated with improved performance in a food-rewarded learning task. Overall, our work identifies a top-down pathway that uses gamma synchronization to guide the activity of subcortical networks and to regulate feeding behaviour by dynamic reorganization of functional cell groups in the hypothalamus.

ABSTRACT

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Among fetuses with AVSD, those with trisomy 21 are detected earlier in pregnancy, have less distorted cardiac anatomy, higher rates of biventricular repair and better survival rates. Due to the limited sample size in euploid fetuses, it remains unclear whether this apparent protection afforded to Down syndrome accounts also for cohorts with isolated and balanced AVSD.

Hippocampal pyramidal cells encode an animal’s location by single action potentials and complex spike bursts. These elementary signals are believed to play distinct roles in memory consolidation. The timing of single spikes and bursts is determined by intrinsic excitability and theta oscillations (5–10 Hz). Yet contributions of these dynamics to place fields remain elusive due to the lack of methods for specific modification of burst discharge. In mice lacking Kcnq3-containing M-type K+ channels, we find that pyramidal cell bursts are less coordinated by the theta rhythm than in controls during spatial navigation, but not alert immobility. Less modulated bursts are followed by an intact post-burst pause of single spike firing, resulting in a temporal discoordination of network oscillatory and intrinsic excitability. Place fields of single spikes in one- and two-dimensional environments are smaller in the mutant. Optogenetic manipulations of upstream signals reveal that neither medial septal GABA-ergic nor cholinergic inputs alone, but rather their joint activity, is required for entrainment of bursts. Our results suggest that altered representations by bursts and single spikes may contribute to deficits underlying cognitive disabilities associated with KCNQ3-mutations in humans.

Zusammenfassung. Die integrative Lerntherapie ist eine adäquate Hilfeform bei Lernstörungen. Sie nutzt wissenschaftliche Erkenntnisse aus der Psychologie und Medizin, den Fachdidaktiken und der Pädagogik sowie der Linguistik und der Mathematik. Kinder, Jugendliche und Erwachsene mit Lernstörungen haben erhebliche Schwierigkeiten beim Erwerb der Schriftsprache und/oder Mathematik. Da Lesen, Schreiben und Rechnen Schlüsselkompetenzen für die gesamte weitere Lernentwicklung sind, sind die Lern- und Bildungsbiografie sowie die gesunde Persönlichkeitsentwicklung der Betroffenen in hohem Maße gefährdet. Sie benötigen eine passende Hilfe, welche die integrative Lerntherapie bietet. Im vorliegenden Beitrag werden die Therapieform sowie deren Komponenten beschrieben. Der Beitrag dient der Etablierung der integrativen Lerntherapie als Behandlungskonzept bei Lernstörungen sowie als Grundlage der interdisziplinären Diskussion sowie der Forschung im Bereich Lernstörungen.

1 The effects of a single oral dose of 5 mg pindolol (P) and 100mg metoprolol (M) were assessed in a double-blind study in 30 patients undergoing oral surgery. 2 Systolic and diastolic blood pressures and heart rate were reduced 90 min after oral medication and did not exceed initial values at rest during the procedure. 3 Noradrenaline, adrenaline and c-AMP concentrations did not differ at any time from the control values at rest after P, but were increased after local anaesthesia and during oral surgery after M as were the metabolic responses reflected by plasma concentrations of glucose and free-fatty acids. 4 Plasma levels of ACTH and cortisol showed the typical increase during the procedure, being independent of ,B-adrenoceptor blockade. In contrast to the cardioselective antagonist M, prophylactic administration of the non-selective drug P prevented the sympathetic and metabolic responses to the stress of oral surgery.5 Hypothalamic and adrenal stimulation were not reduced by either selective or non-selective ,B-adrenoceptor blockade.