Gabaergic

1. The role of gamma-aminobutyric acid (GABA) on the pattern generation properties of neuronal ensembles in the olivocerebellar system was studied utilizing multiple electrode recordings of complex spikes (CSs) from rat crus 2a Purkinje cells (PCs). Initially multiple electrode experiments were combined with microinjections of picrotoxin into the inferior olive (IO). To corroborate the picrotoxin findings, the cerebellar nuclei, a major source of the GABAergic terminals in the IO, were chemically lesioned with the use of microinjections of kainic acid and N-methyl-D-aspartate. Both procedures generated comparable results. 2. After intraolivary picrotoxin injection there was an increase in the average firing rate, synchrony, and rhythmicity of spontaneous CS activity. In addition, the neuronal oscillation frequency tended to shift to lower frequencies. 3. The spatial distribution of synchronous CS activity in control conditions displayed a predominantly rostrocaudal orientation. Inje...

It has been suggested that increased GABAergic innervation in the hippocampus plays a significant role in cognitive dysfunction in Down syndrome (DS). Bolstering this notion, are studies linking hyper-innervation of the dentate gyrus (DG) by GABAergic terminals to failure in LTP induction in the Ts65Dn mouse model of DS. Here, we used extensive morphometrical methods to assess the status of GABAergic interneurons in the DG of young and old Ts65Dn mice and their 2N controls. We detected an age-dependent increase in GABAergic innervation of dentate granule cells (DGCs) in Ts65Dn mice. The primary source of GABAergic terminals to DGCs somata is basket cells (BCs). For this reason, we assessed the status of these cells and found a significant increase in the number of BCs in Ts65Dn mice compared with controls. Then we aimed to identify the gene/s whose overexpression could be linked to increased number of BCs in Ts65Dn and found that deleting the third copy of App gene in Ts65Dn mice led to normalization of the number of BCs in these mice. Our data suggest that App overexpression plays a major role in the pathophysiology of GABAergic hyperinnervation of the DG in Ts65Dn mice.

We have studied the GABAergic projections to the inferior colliculus (IC) of the rat by combining the retrograde transport of horseradish peroxidase (HRP) and immunohistochemistry for gamma-amino butyric acid (GABA). Medium-sized (0.06-0.14 microliter) HRP injections were made in the ventral part of the central nucleus (CNIC), in the dorsal part of the CNIC, in the dorsal cortex (DCIC), and in the external cortex (ECIC) of the IC. Single HRP-labeled and double (HRP-GABA)-labeled neurons were systematically counted in all brainstem auditory nuclei. Our results revealed that the IC receives GABAergic afferent connections from ipsi- and contralateral brainstem auditory nuclei. Most of the contralateral GABAergic input originates in the IC and the dorsal nucleus of the lateral lemniscus (DNLL). The dorsal region of the IC (DCIC and dorsal part of the CNIC) receives connections mostly from its homonimous contralateral region, and the ventral region from the contralateral DNLL. The commissural GABAergic projections originate in a morphologically heterogeneous neuronal population that includes small to medium-sized round and fusiform neurons as well as large and giant neurons. Quantitatively, the ipsilateral ventral nucleus of the lateral lemniscus is the most important source of GABAergic input to the CNIC. In the superior olivary complex, a smaller number of neurons, which lie mainly in the periolivary nuclei, display double labeling. In the contralateral cochlear nuclei, only a few of the retrogradely labeled neurons were GABA immunoreactive. These findings give us more information about the role of GABA in the auditory system, indicating that inhibitory inputs from different ipsi- and contralateral, mono- and binaural auditory brainstem centers converge in the IC.

Synthetic terpenes as a universal  gabaergic, dopaminergic and light cannabinoids. 
  In contrast terpene-glutaminergic, GABA activating terpenes are not represented in nature. Glutaminergic terpenes have a more destructive effect on the Central nervous system, however, included in the composition of the essential oil of wormwood and spices of saffron - stigmas of Crocus sativus. 
Strukture of GABA and glutamic acid are close, and it would be logical to fix to try to replace glutamic features active terpenes on the GABA radicals. At least to get away from the glutamic activity, or even to replace it with GABA activity. What was done on the example of the five-membered derivative of the aglycone picrocrocin (Krokus sativus). Also given the possible recreational potential, was an attempt to make cannabinoid accents, and thus to  probably implementing triple structure recreational activity. Design of multifunctional structures allows to obtain recreational substances with a unique qualities and minimal negative qualities.
In the event the success of the approach and implementation. Like many natural multifunctional substances, such structures can have a future as a legal pharmacological and recreational drugs.
Examples of some derivatives of terpenes:
Синтетические терпены как универсальные ГАМК энергетик, допаминергик и легкие каннабиноиды.
В отличие от терпенов глутаминергической активности, ГАМК активирующие терпены не представлены в природе. Глутаминергические терпены имеют несколько разрушительное влияние на центральную нервную систему, тем не менее входят в состав эфирного масла горькой полыни и приправы шафрана из рылец крокуса шафранного.
Природа ГАМК и глутаминовой кислоты близка, и логичной была бы попытка заменить глутаминовые черты активных терпенов на ГАМК радикалы. Как минимум уйти от глутаминовой активности, или даже заменить её на ГАМК активность. Что и было сделано на примере пятичленного производного агликона пикрокроцина (крокус посевной). Также учитывая возможный рекреационный потенциал, были внесены и каннабиноидные акценты, таким образом чтобы получить структуры вероятно c тройным  рекреационным действием. Дизайн многофункциональных структур позволяет получать рекреационные вещества с уникальными показателями и минимальными негативными качествами.
При успешности подхода и реализации, подобно многим природным многофункциональным веществам, такие структуры могут иметь будущее как легальные фармакологические и рекреационные препараты.
Примеры некоторых производных терпенов: