Encoding and retrieval in a CA1 microcircuit model of the hippocampus

Recent years have witnessed a dramatic accumulation of knowledge about the morphological, physiological and molecular characteristics, as well as connectivity and synaptic properties of neurons in the mammalian hippocampus. Despite these advances, very little insight has been gained into the computational function of the different neuronal classes; in particular, the role of the various inhibitory interneurons in encoding and retrieval of information remains elusive. Mathematical and computational models of microcircuits play an instrumental role in exploring microcircuit functions and facilitate the dissection of operations performed by diverse inhibitory interneurons. A model of the CA1 microcircuitry is presented using biophysical representations of its major cell types: pyramidal, basket, axo-axonic, bistratified and oriens lacunosummoleculare cells. Computer simulations explore the biophysical mechanisms by which encoding and retrieval of spatio-temporal input patterns are achieved by the CA1 microcircuitry. The model proposes functional roles for the different classes of inhibitory interneurons in the encoding and retrieval cycles

Involvement of a glibenclamide-sensitive mechanism in the nitrergic neurotransmission of the pig intravesical ureter

1. The present study was designed to investigate whether potassium (K(+)) channels are involved in the relaxations to nitric oxide (NO) of pig intravesical ureteral preparations suspended in organ baths for isometric tension recordings. In ureteral strips treated with guanethidine (10(−5) M) and atropine (10(−7) M) to block adrenergic neurotransmission and muscarinic receptors, respectively, NO was either released from nitrergic nerves by electrical field stimulation (EFS, 0.5–10 Hz, 1 ms duration, 20 s trains), or exogenously-applied as an acidified solution of sodium nitrite (NaNO(2), 10(−6)–10(−3) M). 2. Incubation with an inhibitor of guanylate cyclase activation by NO, methylene blue (10(−5) M) did not change the basal tension of intravesical ureteral strips but inhibited the relaxation induced by EFS or exogenous NO on ureteral preparations contracted with the thromboxane analogue U46619 (10(−7) M). 3. Incubation with charybdotoxin (3×10(−8) M) and apamin (5×10(−7) M), which are inhibitors of large and small conductance calcium (Ca(2+))-activated K(+) channels, respectively, did not modify basal tension or the relaxations induced by EFS and exogenous NO. Treatment with charybdotoxin or apamin plus methylene blue (10(−5) M) significantly reduced the relaxations to EFS and exogenous NO. However, in both cases the reductions were similar to the inhibition evoked by methylene blue alone. The combined addition of charybdotoxin plus apamin did not change the relaxations to EFS or exogenously added NO of the porcine intravesical ureter. 4. Cromakalim (10(−8)–3×10(−6) M), an opener of ATP-sensitive K(+) channels, evoked a dose-dependent relaxation with a pD(2) of 7.3±0.2 and maximum relaxant effect of a 71.8±4.2% of the contraction induced by U46619 in the pig intravesical ureter. The blocker of ATP-sensitive K(+) channels, glibenclamide (10(−6) M), inhibited markedly the relaxations to cromakalim. 5. Glibenclamide (10(−6) M) had no effect on the basal tone of ureteral preparations but significantly reduced the relaxations induced by both EFS and exogenous NO. Combined treatment with methylene blue (10(−5) M) and glibenclamide (10(−6) M) did not exert an effect greater than that of methylene blue alone on either EFS- or NO-evoked relaxations of the pig ureter. 6. The present results suggest that NO acts as an inhibitory neurotransmitter in the pig intravesical ureter and relaxes smooth muscle through a guanylate cyclase-dependent mechanism which seems to favour the opening of glibenclamide-sensitive K(+) channels

A(2B) adenosine receptors mediate relaxation of the pig intravesical ureter: adenosine modulation of non adrenergic non cholinergic excitatory neurotransmission

1. The present study was designed to characterize the adenosine receptors involved in the relaxation of the pig intravesical ureter, and to investigate the action of adenosine on the non adrenergic non cholinergic (NANC) excitatory ureteral neurotransmission. 2. In U46619 (10(−7)  M)-contracted strips treated with the adenosine uptake inhibitor, nitrobenzylthioinosine (NBTI, 10(−6)  M), adenosine and related analogues induced relaxations with the following potency order: 5′-N-ethylcarboxamidoadenosine (NECA)=5′-(N-cyclopropyl)-carboxamidoadenosine (CPCA)=2-chloroadenosine (2-CA)>adenosine>cyclopentyladenosine (CPA)=N(6)-(3-iodobenzyl)-adenosine-5′-N-methylcarboxamide (IB-MECA)=2-[p-(carboxyethyl)-phenylethylamino]-5′-N-ethylcarboxamidoadenosine (CGS21680). 3. Epithelium removal or incubation with indomethacin (3×10(−6)  M) and L-N(G)-nitroarginine (L-NOARG, 3×10(−5)  M), inhibitors of prostanoids and nitric oxide (NO) synthase, respectively, failed to modify the relaxations to adenosine. 4. 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10(−8) M) and 4-(2-[7-amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM 241385, 3×10(−8)  M and 10(−7)  M), A(1) and A(2A) receptor selective antagonists, respectively, did not modify the relaxations to adenosine or NECA. 8-phenyltheophylline (8-PT, 10(−5)  M) and DPCPX (10(−6)  M), which block A(1)/A(2)-receptors, reduced such relaxations. 5. In strips treated with guanethidine (10(−5)  M), atropine (10(−7)  M), L-NOARG (3×10(−5)  M) and indomethacin (3×10(−6)  M), both electrical field stimulation (EFS, 5 Hz) and exogenous ATP (10(−4)  M) induced contractions of preparations. 8-PT (10(−5)  M) increased both contractions. DPCPX (10(−8)  M), NECA (10(−4)  M), CPCA, (10(−4)  M) and 2-CA (10(−4)  M) did not alter the contractions to EFS. 6. The present results suggest that adenosine relaxes the pig intravesical ureter, independently of prostanoids or NO, through activation of A(2B)-receptors located in the smooth muscle. This relaxation may modulate the ureteral NANC excitatory neurotransmission through a postsynaptic mechanism