Sonic Hedgehog is expressed by hilar mossy cells and regulates cellular survival and neurogenesis in the adult hippocampus.

Sonic hedgehog (Shh) is a multifunctional signaling protein governing pattern formation, proliferation and cell survival during embryogenesis. In the adult brain, Shh has neurotrophic function and is implicated in hippocampal neurogenesis but the cellular source of Shh in the hippocampus remains ill defined. Here, we utilize a gene expression tracer allele of Shh (Shh-nlacZ) which allowed the identification of a subpopulation of hilar neurons known as mossy cells (MCs) as a prominent and dynamic source of Shh within the dentate gyrus.

Self-propagating, non-synaptic epileptiform activity recruits neurons by endogenous electric fields.

It is well documented that synapses play a significant role in the transmission of information between neurons. However, in the absence of synaptic transmission, neural activity has been observed to continue to propagate. Previous studies have shown that propagation of epileptiform activity takes place in the absence of synaptic transmission and gap junctions and is outside the range of ionic diffusion and axonal conduction.

Slow periodic activity in the longitudinal hippocampal slice can self-propagate non-synaptically by a mechanism consistent with ephaptic coupling.

Key Points: Slow periodic activity can propagate with speeds around 0.1 m s and be modulated by weak electric fields. Slow periodic activity in the longitudinal hippocampal slice can propagate without chemical synaptic transmission or gap junctions, but can generate electric fields which in turn activate neighbouring cells.

Slow moving neural source in the epileptic hippocampus can mimic progression of human seizures.

Fast and slow neural waves have been observed to propagate in the human brain during seizures. Yet the nature of these waves is difficult to study in a surgical setting. Here, we report an observation of two different traveling waves propagating in the in-vitro epileptic hippocampus at speeds similar to those in the human brain.

Propagating Neural Source Revealed by Doppler Shift of Population Spiking Frequency.

Unlabelled: Electrical activity in the brain during normal and abnormal function is associated with propagating waves of various speeds and directions. It is unclear how both fast and slow traveling waves with sometime opposite directions can coexist in the same neural tissue. By recording population spikes simultaneously throughout the unfolded rodent hippocampus with a penetrating microelectrode array, we have shown that fast and slow waves are causally related, so a slowly moving neural source generates fast-propagating waves at ∼0.

Seizure reduction through interneuron-mediated entrainment using low frequency optical stimulation.

Low frequency electrical stimulation (LFS) can reduce neural excitability and suppress seizures in animals and patients with epilepsy. However the therapeutic outcome could benefit from the determination of the cell types involved in seizure suppression. We used optogenetic techniques to investigate the role of interneurons in LFS (1Hz) in the epileptogenic hippocampus.

Seizure suppression by high frequency optogenetic stimulation using in vitro and in vivo animal models of epilepsy.

Background: Electrical high frequency stimulation (HFS) has been shown to suppress seizures. However, the mechanisms of seizure suppression remain unclear and techniques for blocking specific neuronal populations are required.

Objective: The goal is to study the optical HFS protocol on seizures as well as the underlying mechanisms relevant to the HFS-mediated seizure suppression by using optogenetic methodology.

Propagation of epileptiform activity can be independent of synaptic transmission, gap junctions, or diffusion and is consistent with electrical field transmission.

The propagation of activity in neural tissue is generally associated with synaptic transmission, but epileptiform activity in the hippocampus can propagate with or without synaptic transmission at a speed of ∼0.1 m/s. This suggests an underlying common nonsynaptic mechanism for propagation.

TRPV1 antagonist capsazepine suppresses 4-AP-induced epileptiform activity in vitro and electrographic seizures in vivo.

Transient receptor potential vanilloid 1 (TRPV1) is a cation-permeable ion channel found in the peripheral and central nervous systems. The membrane surface expression of TRPV1 is known to occur in neuronal cell bodies and sensory neuron axons. TRPV1 receptors are also expressed in the hippocampus, the main epileptogenic region in the brain.

Sonic hedgehog maintains cellular and neurochemical homeostasis in the adult nigrostriatal circuit.

Non cell-autonomous processes are thought to play critical roles in the cellular maintenance of the healthy and diseased brain but mechanistic details remain unclear. We report that the interruption of a non cell-autonomous mode of sonic hedgehog (Shh) signaling originating from dopaminergic neurons causes progressive, adult-onset degeneration of dopaminergic, cholinergic, and fast spiking GABAergic neurons of the mesostriatal circuit, imbalance of cholinergic and dopaminergic neurotransmission, and motor deficits reminiscent of Parkinson's disease. Variable Shh signaling results in graded inhibition of muscarinic autoreceptor- and glial cell line-derived neurotrophic factor (GDNF)-expression in the striatum.