Internal-state-dependent control of feeding behavior via hippocampal ghrelin signaling.

Hunger is an internal state that not only invigorates feeding but also acts as a contextual cue for higher-order control of anticipatory feeding-related behavior. The ventral hippocampus is crucial for differentiating optimal behavior across contexts, but how internal contexts such as hunger influence hippocampal circuitry is unknown. In this study, we investigated the role of the ventral hippocampus during feeding behavior across different states of hunger in mice. We found that activity of a unique subpopulation of neurons that project to the nucleus accumbens (vS-NAc neurons) increased when animals investigated food, and this activity inhibited the transition to begin eating. Increases in the level of the peripheral hunger hormone ghrelin reduced vS-NAc activity during this anticipatory phase of feeding via ghrelin-receptor-dependent increases in postsynaptic inhibition and promoted the initiation of eating. Together, these experiments define a ghrelin-sensitive hippocampal circuit that informs the decision to eat based on internal state.

Deep phenotyping of frontal lobe epilepsy compared to other epilepsy syndromes.

AIMS: Frontal lobe epilepsy (FLE) is understudied and often misdiagnosed. We sought to comprehensively phenotype FLE and to differentiate FLE from other focal and generalised epilepsy syndromes. METHODS: This was a retrospective, observational cohort study of 1078 cases of confirmed epilepsy in a tertiary neurology centre in London. Data sources were electronic health records, investigation reports and clinical letters. RESULTS: 166 patients had FLE based on clinical findings and investigations-97 with identifiable electroencephalography (EEG) foci in frontal areas (definite FLE), while 69 had no frontal EEG foci (probable FLE). Apart from EEG findings, probable and definite FLE did not differ in other features. FLE was distinct from generalized epilepsy, which tended to present with tonic-clonic seizures and be due to genetic causes. FLE and temporal lobe epilepsy (TLE) both featured focal unaware seizures and underlying structural or metabolic aetiology. FLE, TLE and generalized epilepsy differed in their EEG (P = 0.0003) and MRI (P = 0.002) findings, where FLE had a higher rate of normal EEG and abnormal MRI findings compared to TLE. CONCLUSIONS: EEG is often normal for FLE, and abnormalities are commonly identified with MRI. There was no difference in the clinical features of definite and probable FLE, suggesting they represent the same clinical entity. The diagnosis of FLE can be made even when scalp EEG is normal. This large medical cohort provides hallmark features of FLE that differentiate it from TLE and other epilepsy syndromes.

Two opposing hippocampus to prefrontal cortex pathways for the control of approach and avoidance behaviour.

The decision to either approach or avoid a potentially threatening environment is thought to rely upon the coordinated activity of heterogeneous neural populations in the hippocampus and prefrontal cortex (PFC). However, how this circuitry is organized to flexibly promote both approach or avoidance at different times has remained elusive. Here, we show that the hippocampal projection to PFC is composed of two parallel circuits located in the superficial or deep pyramidal layers of the CA1/subiculum border. These circuits have unique upstream and downstream connectivity, and are differentially active during approach and avoidance behaviour. The superficial population is preferentially connected to widespread PFC inhibitory interneurons, and its activation promotes exploration; while the deep circuit is connected to PFC pyramidal neurons and fast spiking interneurons, and its activation promotes avoidance. Together this provides a mechanism for regulation of behaviour during approach avoidance conflict: through two specialized, parallel circuits that allow bidirectional hippocampal control of PFC.

Biased Connectivity of Brain-wide Inputs to Ventral Subiculum Output Neurons.

The ventral subiculum (vS) of the mouse hippocampus coordinates diverse behaviors through heterogeneous populations of pyramidal neurons that project to multiple distinct downstream regions. Each of these populations of neurons is proposed to integrate a unique combination of thousands of local and long-range synaptic inputs, but the extent to which this occurs remains unknown. To address this, we employ monosynaptic rabies tracing to study the input-output relationship of vS neurons. Analysis of brain-wide inputs reveals quantitative input differences that could be explained by a combination of both the identity of the downstream target and the spatial location of the postsynaptic neurons within vS. These results support a model of combined topographical and output-defined connectivity of vS inputs. Overall, we reveal prominent heterogeneity in brain-wide inputs to the vS parallel output circuitry, providing a basis for the selective control of individual projections during behavior.