Piriform cortex is an ictogenic trigger zone in the primate brain.

Objective: Area tempestas, a functionally defined region in the anterior piriform cortex, was identified as a crucial ictogenic trigger zone in the rat brain in the 1980s. However, whether the primate piriform cortex can trigger seizures remains unknown. Here, in a nonhuman primate model, we aimed to localize a similar trigger zone in the piriform cortex and, subsequently, evaluated the ability of focal inhibition of the substantia nigra pars reticulata (SNpr) to suppress the evoked seizures.

The Effect of Traumatic Brain Injury on Sleep Architecture and Circadian Rhythms in Mice-A Comparison of High-Frequency Head Impact and Controlled Cortical Injury.

Traumatic brain injury (TBI) is a significant risk factor for the development of sleep and circadian rhythm impairments. In this study we compare the circadian rhythms and sleep patterns in the high-frequency head impact (HFHI) and controlled cortical impact (CCI) mouse models of TBI. These mouse models have different injury mechanisms key differences of pathology in brain regions controlling circadian rhythms and EEG wave generation.

Pathway-specific inhibition of critical projections from the mediodorsal thalamus to the frontal cortex controls kindled seizures.

There is a large unmet need for improved treatment for temporal lobe epilepsy (TLE); circuit-specific manipulation that disrupts the initiation and propagation of seizures is promising in this regard. The midline thalamus, including the mediodorsal nucleus (MD) is a critical distributor of seizure activity, but its afferent and efferent pathways that mediate seizure activity are unknown. Here, we used chemogenetics to silence input and output projections of the MD to discrete regions of the frontal cortex in the kindling model of TLE in rats.

Optogenetic activation of the reticular nucleus of the thalamus attenuates limbic seizures via inhibition of the midline thalamus.

Objective: The nucleus reticularis of the thalamus (nRT) is most studied in epilepsy for its role in the genesis of absence seizures; much less is known regarding its role in other seizure types, including those originating in limbic structures and the temporal lobe. As it is a major source of inhibitory input to higher order thalamic nuclei, stimulation of the nRT may be an effective strategy to disrupt seizure activity that requires thalamic engagement.

Methods: We recorded single unit activity from the nRT prior to and after infusion of bicuculline into the area tempestas.

Divergent Effects of Systemic and Intracollicular CB Receptor Activation Against Forebrain and Hindbrain-Evoked Seizures in Rats.

Cannabinoid (CB) receptor agonists are of growing interest as targets for anti-seizure therapies. Here we examined the effect of systemic administration of the CB receptor agonist WIN 55,212-2 (WIN) against audiogenic seizures (AGSs) in the Genetically Epilepsy Prone Rat (GEPR)-3 strain, and against seizures evoked focally from the (AT). We compared these results to the effect of focal administration of the CB1/2 receptor agonist CP 55940 into the deep layers of the superior colliculus (DLSC), a brain site expressing CB1 receptors.

Serum Amyloid A is Expressed in the Brain After Traumatic Brain Injury in a Sex-Dependent Manner.

Serum amyloid A (SAA) is an acute phase protein upregulated in the liver after traumatic brain injury (TBI). So far, it has not been investigated whether SAA expression also occurs in the brain in response to TBI. For this, we performed a moderate controlled cortical impact injury in adult male and female mice and analyzed brain, blood, and liver samples at 6 h, 1, 3, and 10 days post-injury (dpi).

Descending projections from the differentially control seizures.

Three decades of studies have shown that inhibition of the (SNpr) attenuates seizures, yet the circuits mediating this effect remain obscure. SNpr projects to the deep and intermediate layers of the superior colliculus (DLSC) and the pedunculopontine nucleus (PPN), but the contributions of these projections are unknown. To address this gap, we optogenetically silenced cell bodies within SNpr, nigrotectal terminals within DLSC, and nigrotegmental terminals within PPN.

Serum Amyloid A Protein as a Potential Biomarker for Severity and Acute Outcome in Traumatic Brain Injury.

Traumatic brain injury (TBI) causes a wide variety of neuroinflammatory events. These neuroinflammatory events depend, to a greater extent, on the severity of the damage. Our previous studies have shown that the liver produces serum amyloid A (SAA) at high levels in the initial hours after controlled cortical impact (CCI) injury in mice.

Mediodorsal thalamus is required for discrete phases of goal-directed behavior in macaques.

Reward contingencies are dynamic: outcomes that were valued at one point may subsequently lose value. Action selection in the face of dynamic reward associations requires several cognitive processes: registering a change in value of the primary reinforcer, adjusting the value of secondary reinforcers to reflect the new value of the primary reinforcer, and guiding action selection to optimal choices. Flexible responding has been evaluated extensively using reinforcer devaluation tasks.

Anticonvulsant effect of cannabinoid receptor agonists in models of seizures in developing rats.

Objective: Although drugs targeting the cannabinoid system (e.g., CB1 receptor agonists) display anticonvulsant efficacy in adult animal models of seizures/epilepsy, they remain unexplored in developing animal models.

Chemogenetic silencing of the midline and intralaminar thalamus blocks amygdala-kindled seizures.

Temporal lobe epilepsy is the most common form of medically-intractable epilepsy. While seizures in TLE originate in structures such as hippocampus, amygdala, and temporal cortex, they propagate through a crucial relay: the midline/intralaminar thalamus. Prior studies have shown that pharmacological inhibition of midline thalamus attenuates limbic seizures.

Optogenetic activation of superior colliculus neurons suppresses seizures originating in diverse brain networks.

Because sites of seizure origin may be unknown or multifocal, identifying targets from which activation can suppress seizures originating in diverse networks is essential. We evaluated the ability of optogenetic activation of the deep/intermediate layers of the superior colliculus (DLSC) to fill this role. Optogenetic activation of DLSC suppressed behavioral and electrographic seizures in the pentylenetetrazole (forebrain+brainstem seizures) and Area Tempestas (forebrain/complex partial seizures) models; this effect was specific to activation of DLSC, and not neighboring structures.