Distinct Corticostriatal GABAergic Neurons Modulate Striatal Output Neurons and Motor Activity.

The motor cortico-basal ganglion loop is critical for motor planning, execution, and learning. Balanced excitation and inhibition in this loop is crucial for proper motor output. Excitatory neurons have been thought to be the only source of motor cortical input to the striatum. Here, we identify long-range projecting GABAergic neurons in the primary (M1) and secondary (M2) motor cortex that target the dorsal striatum. This population of projecting GABAergic neurons comprises both somatostatin-positive (SOM+) and parvalbumin-positive (PV+) neurons that target direct and indirect pathway striatal output neurons as well as cholinergic interneurons differentially. Notably, optogenetic stimulation of M1 PV+ and M2 SOM+ projecting neurons reduced locomotion, whereas stimulation of M1 SOM+ projecting neurons enhanced locomotion. Thus, corticostriatal GABAergic projections modulate striatal output and motor activity.

The long and short of GABAergic neurons.

GABA (γ-aminobutyric acid) is the primary inhibitory neurotransmitter in the adult brain. Studies on GABAergic cells have focused almost exclusively on local interneurons neglecting those inhibitory neurons projecting to different brain areas, the 'long-range GABAergic cells'. This review focuses on some common features and peculiarities of 'corticofugal' and 'corticopetal' GABAergic cells. Similarly to their local counterpart, long-range GABAergic cells show immunohistochemical diversity and contact locally both excitatory and inhibitory cells. Distally, long-range GABAergic cells often target other inhibitory neurons. This feature endows them with the ability to control remote target areas via disinhibition. On the basis of few functional studies that investigated their participation in synchronous network activity, we propose that long-range GABAergic neurons play a critical role in the temporal coordination of neuronal activity in distant brain areas.

Long-range-projecting GABAergic neurons modulate inhibition in hippocampus and entorhinal cortex.

The hippocampus and entorhinal cortex play a pivotal role in spatial learning and memory. The two forebrain regions are highly interconnected via excitatory pathways. Using optogenetic tools, we identified and characterized long-range γ-aminobutyric acid-releasing (GABAergic) neurons that provide a bidirectional hippocampal-entorhinal inhibitory connectivity and preferentially target GABAergic interneurons. Activation of long-range GABAergic axons enhances sub- and suprathreshold rhythmic theta activity of postsynaptic neurons in the target areas.

Treatment of acute migraine headache.

Migraine headache is a common and potentially debilitating disorder often treated by family physicians. Before diagnosing migraine, serious intracranial pathology must be ruled out. Treating acute migraine is challenging because of substantial rates of nonresponse to medications and difficulty in predicting individual response to a specific agent or dose. Data comparing different drug classes are relatively scarce. Abortive therapy should be used as early as possible after the onset of symptoms. Effective first-line therapies for mild to moderate migraine are nonprescription nonsteroidal anti-inflammatory drugs and combination analgesics containing acetaminophen, aspirin, and caffeine. Triptans are first-line therapies for moderate to severe migraine, or mild to moderate migraine that has not responded to adequate doses of simple analgesics. Triptans should be avoided in patients with vascular disease, uncontrolled hypertension, or hemiplegic migraine. Intravenous antiemetics, with or without intravenous dihydroergotamine, are effective therapies in an emergency department setting. Dexamethasone may be a useful adjunct to standard therapy in preventing short-term headache recurrence. Intranasal lidocaine may also have a role in relief of acute migraine. Isometheptene-containing compounds and intranasal dihydroergotamine are also reasonable therapeutic options. Medications containing opiates or barbiturates should be avoided for acute migraine. During pregnancy, migraine may be treated with acetaminophen or nonsteroidal anti-inflammatory drugs (prior to third trimester), or opiates in refractory cases. Acetaminophen, ibuprofen, intranasal sumatriptan, and intranasal zolmitriptan seem to be effective in children and adolescents, although data in these age groups are limited.