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Department of Molecular and Integrative Physiology; Department of Pharmacology, College of Medicine; and Beckman Institute, University of Illinois, Urbana-Champaign, Urbana, Illinois
Submitted 4 December 2006; accepted in final form 15 March 2007
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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; Livingstone and Hubel 1981) and to the spatial and temporal integration of ascending sensory signals (Berardi and Morrone 1984; Cox and Sherman 2000; Norton and Godwin 1992; Zhu and Uhlrich 1997). In addition to altering sensory information processing, inhibitory mechanisms play an important role in various intrathalamic rhythmic activities associated with different arousal states and pathophysiological conditions such as absence epilepsy (Cox et al. 1997a; Kim et al. 1997; McCormick 2002; Steriade et al. 1993; von Krosigk et al. 1993).
Nitric oxide (NO) has the unconventional characteristic of being a gaseous neurotransmitter (Boehning and Snyder 2003; Garthwaite et al. 1988). Unlike classical neurotransmitters, which are generally spatially restricted near the synapse, NO can behave hormonelike because it can freely move through membranes and influence neighboring neurons several hundred microns away (Garthwaite and Boulton 1995; Park et al. 1998). NO was previously found to produce a variety of actions in the nervous system by altering neuronal excitability and synaptic transmission through modulation of cGMP and S-nitrosylation (Ahern et al. 2002).
Although NO was found to produce a wide variety of actions in many brain regions, NO-mediated actions in the thalamus are predominantly excitatory (Cudeiro and Rivadulla 1999; Salt and Pape 1999). Nitric oxide synthase (NOS), the enzyme required for NO production, is localized within GABAergic dLGN interneurons and TRN neurons and within acetylcholine-containing neurons in mesopontine tegmental nuclei neurons that innervate most thalamic nuclei (Carden et al. 2000; Erisir et al. 1997; Gabbott and Bacon 1994; McCauley et al. 2002, 2003). The NO-releasing compound SIN-1 selectively depolarizes thalamocortical relay neurons by shifting the activation curve of the hyperpolarization-activated mixed cation current Ih (Pape and Mager 1992). Previously NO was shown to selectively potentiate N-methyl-D-aspartate (NMDA)–dependent excitatory synaptic responses arising from corticogeniculate afferents in vitro (Alexander et al. 2006). In vivo, the NO precursor L-arginine, the NO donor SIN-1, and cyclic-GMP analogue 8-Br-cGMP potentiate sensory-evoked responses (Do et al. 1994; Shaw and Salt 1997; Shaw et al. 1999). Within the visual system the NO donor SNAP selectively potentiates visual responses mediated by NMDA glutamatergic receptors (Cudeiro and Rivadulla 1999; Cudeiro et al. 1994). Furthermore, extracellular NO concentrations in thalamus are positively correlated with arousal levels, suggesting a putative role in regulating the excitability state of thalamic neurons (Marino and Cudeiro 2003; Williams et al. 1997). Despite the existing work indicating alteration in neuronal excitation and excitatory synaptic transmission, the role of NO in the regulation/modulation of inhibitory activity remains unexplored.
NOS is highly localized in 
-aminobutyric acid (GABA)–containing thalamic neurons as well as afferent cholinergic fibers. In addition, the increase in NO was previously associated with increased GABA release by presynaptic mechanisms in the paraventricular and supraoptic nucleus (Kraus and Prast 2002; Li et al. 2002, 2004; Ohkuma et al. 1998; Ozaki et al. 2000; Yu and Eldred 2005). Considering the thalamic NOS localization and NO-mediated influences on inhibitory activity elsewhere, we sought to test the putative role of NO on inhibitory activity within the thalamus. In addition to reports regarding excitatory actions of NO in thalamus, alterations in inhibitory activity could have a significant influence on accurate visual information transfer. Our results indicate that increasing NO levels potentiated inhibitory activity, presumably increasing GABA release from presynaptic terminals by a cGMP-dependent process. Such an action was further potentiated by the depolarization of TRN, thereby increasing the inhibitory tone in thalamocortical neurons.
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METHODS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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Sprague–Dawley rats (postnatal age: 10–16 days) were deeply anesthetized with sodium pentobarbital (55 mg/kg); the brains were quickly removed and placed into chilled (4°C), oxygenated (5% CO2-95% O2) slicing medium containing (in mM): 2.5 KCl, 1.25 NaH2PO4, 10.0 MgSO4, 0.5 CaCl2, 26.0 NaHCO3, 11.0 glucose, and 234.0 sucrose. Slices (300 µm thick) were cut using a vibrating tissue slicer in the coronal plane for dLGN recordings and in the horizontal plane for ventrobasal nucleus (VB) and TRN recordings. Slices were then transferred to a holding chamber containing oxygenated physiological saline that contained (in mM): 126.0 NaCl, 2.5 KCl, 1.25 NaH2PO4, 2.0 MgCl2, 2.0 CaCl2, 26.0 NaHCO3, and 10.0 glucose. Individual slices were then transferred to a recording chamber maintained at 32°C and oxygenated physiological saline was continuously superfused at a rate of 2.0 ml/min.
Intracellular recording procedures
Intracellular recordings were obtained using the whole cell configuration. Recording pipettes had tip resistances of 3–7 M
when filled with a solution containing (in mM): 117.0 Cs-gluconate, 13.0 CsCl, 1.0 MgCl2, 0.07 CaCl2, 0.1 EGTA, 10.0 HEPES, 2.0 Na2-ATP, 0.4 Na-GTP, and 0.3% biocytin. The pH and osmolarity of the intracellular solution was adjusted to 7.3 and 290 mOsm, respectively. The internal solution resulted in a junction potential of approximately 10 mV that was corrected in the voltage measures. A fixed-stage microscope (Axiskop2, Carl Zeiss) equipped with differential interference contrast optics and a x63 water-immersion objective was used to view individual neurons within the slice. Inhibitory synaptic currents were recorded using an Axoclamp 2B amplifier (Molecular Devices, Sunnyvale, CA) in the continuous voltage-clamp mode and a holding potential of 0 mV. Only neurons with stable access resistances <15 M were included in this study. In current-clamp recordings, K+ was substituted for Cs+ in the pipette solution. Membrane voltage was recorded using an Axoclamp 2B amplifier in bridge mode and the active bridge circuit was continuously adjusted to balance the drop in potential produced by passing current through the recording electrode.
Pharmacological agents
Concentrated stock solutions of various pharmacological agents were initially prepared and then diluted in physiological saline to a final concentration before use. Concentrated stocks of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and 3-isobutyl-1-methylxanthine (IBMX) were initially prepared in DMSO. The final DMSO concentration never exceeded 0.1% and this DMSO concentration alone did not produce any alterations in synaptic activity. N-(Acetyloxy)-3-nitrosothiovaline (SNAP) was freshly prepared each day at a final concentration in physiological solution. Agonists were applied by a short-duration (1- to 2-min) bolus into the input line of the recording chamber using a syringe pump. All antagonists were bath applied. L-Arginine, SNAP, NG-monomethyl-L-arginine acetate (L-NMMA), 2-(3-carboxypropyl)-3-amino-6-methoxyphenyl-pyridazinium bromide (SR95531), 2-(4-carboxyphenyl)-4,4,5,5-tetramethylinmidazoline-1-oxide (PTIO), ODQ, TTX, and 8-bromo-guanosine cyclic 3',5'-monophosphate sodium salt (8-Br-cGMP) were purchased from Tocris (Ellisville, MO). IBMX, 8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphorothioate, and Rp isomer triethylammonium (Rp-CPT-cGMP) were purchased from Sigma (St. Louis, MO).
Data acquisition and analyses
Spontaneous synaptic events were digitized and stored using pCLAMP software (Molecular Devices, Sunnyvale, CA) and analyzed off-line using Mini Analysis software (Synaptosoft, Leonia, NJ). The detection of ISPCs was accomplished by setting a threshold above the baseline level in the presence of the GABAA antagonist SR95531. Cumulative probability plots were calculated from 30-s windows just before drug application (control) and during the peak drug response, which typically reached a maximum effect approximately 2 min after drug application and leveled off for 
3 min. The interval across experimental conditions (e.g., in the presence of an antagonist) was constant across experiments. A Kolmogorov–Smirnov (KS) test was used to test statistical significance between different experimental conditions. Histograms illustrating sIPSC frequency and amplitude for individual experiments (e.g., Fig. 1A) were constructed using 5-s bins. Time plots illustrating the population data regarding sIPSC frequency and amplitude were constructed using 30-s bins and then normalized to the predrug baseline level that was calculated from the 3 min before drug application (e.g., Fig. 1C). For population data presented as bar graphs, IPSC frequency and amplitude measurements were calculated from 2-min periods before drug application and during the peak drug response. The values for "wash" were calculated from 2-min periods just before the addition of an antagonist or TTX (e.g., see Fig. 1A). Data are presented as means ± SE. Most statistical analyses consisted of a Student's t-test unless noted otherwise.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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GABAergic innervation of dLGN relay neurons arises from TRN neurons and local dLGN interneurons. We next tested whether SNAP altered the excitability of TRN neurons or dLGN interneurons. Current-clamp recordings were obtained from 15 TRN neurons that had an average resting membrane potential of –79.0 ± 3.8 mV and apparent input resistance of 167.8 ± 36.6 M. SNAP (500 µM) produced a long-lasting depolarization that averaged 3.6 ± 1.2 mV in 13 of 15 neurons tested (Fig. 2A). The depolarization recovered to baseline levels within 14 min. We next obtained current-clamp recordings from four dLGN interneurons. These neurons were differentiated by their unique intrinsic properties and post hoc from their distinct morphology (Govindaiah and Cox 2004; Pape and McCormick 1995; Williams et al. 1996). Interneurons had a lower resting membrane potential of –64.3 ± 5.0 mV (P < 0.01, paired t-test) and a greater input resistance averaging 461.5 ± 121.2 M (P < 0.01, paired t-test) compared with TRN neurons. In the interneurons, SNAP (500 µM) did not alter the membrane potential or input resistance (Fig. 2B, n = 4), indicating that the SNAP-mediated increase in sIPSC frequency in relay neurons could result from suprathreshold excitation of TRN neurons.
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; Govindaiah and Cox 2004).
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NO was previously reported to engage multiple intracellular messenger systems including the guanylyl cyclase (GC)/cGMP pathway (Boehning and Snyder 2003; Bredt and Snyder 1989). We next tested whether the guanylyl cyclase inhibitor ODQ could attenuate the SNAP-mediated facilitation of inhibitory activity. In TTX (0.5 µM), SNAP (500 µM) produced a significant increase in sIPSC frequency that averaged 140.9 ± 10.8% of baseline levels (Fig. 6A, P < 0.01, paired t-test, n = 7). The subsequent SNAP application in ODQ failed to alter sIPSC frequency (Fig. 6A, 98.6 ± 7.5%, P > 0.1, paired t-test, n = 7). The addition of ODQ (100 µM) alone did not alter sIPSC activity (Fig. 6Aii, P > 0.1, paired t-test). These results suggest that NO exerts its effect through activation of soluble guanylyl cyclase (sGC) to increase the cGMP levels in thalamus.
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; Yawo 1999), 8Br-cGMP (50 µM) produced a significant potentiation in sIPSC frequency (Fig. 6B, ii and iv, 139.0 ± 11.4%, P < 0.01, paired t-test, n = 8), which did not reverse within 30 min after drug application. IBMX (100 µM) alone, before 8Br-cGMP application, did not significantly alter sIPSC frequency (98.0 ± 6.5%, n = 21, P > 0.1, paired t-test). Increasing the 8Br-cGMP concentration to 1 mM in the presence of IBMX produced a shorter-latency facilitation with a maximum effect similar to that of the lower 8Br-cGMP concentration (Fig. 6B, iii and iv, 135.0 ± 12.3%, n = 13, P < 0.01, paired t-test).
One of the targets for cGMP activity is the cGMP-stimulated protein kinase G (PKG) (Jaffrey and Snyder 1995) and this pathway is involved with increased GABA release in the paraventricular nucleus (Li et al. 2004). Furthermore, type II cyclic-GMP–dependent protein kinase was previously reported to be highly distributed in thalamus, so we next tested whether the membrane-permeable PKG inhibitor Rp-pCPT-cGMP could attenuate the 8Br-cGMP–mediated increase in sIPSC frequency (Bladen et al. 1996; El Husseini et al. 1999). In the presence of Rp-pCPT-cGMP (5 µM) and IBMX (100 µM), 8Br-cGMP (1 mM) still produced a significant increase in sIPSC frequency (126.9 ± 7.5%, n = 4, P < 0.01, paired t-test) and this increase did not differ from the 8Br-cGMP–mediated facilitation in control conditions (P > 0.05).
Our data strongly indicate that activation of the NO system enhances inhibitory activity by a presynaptic mechanism. Inhibitory innervation of dLGN relay neurons arises from three sources. The local circuit interneurons innervated relay neurons by presynaptic dendrites (named F2 terminals) and axon terminals (named F1 terminals) (Famiglietti Jr and Peters 1972; Guillery 1969; Hamos et al. 1985; Montero 1986; Ralston 1971). TRN neurons also innervate relay neurons by axonal terminals (F1 terminals). To distinguish these two sources of innervation (interneuron vs. TRN neuron), we next recorded from ventrobasal nucleus (VB), a structure that contains very few GABAergic local circuit interneurons in rodents and therefore lacks F2 terminals (Arcelli et al. 1997; Ottersen and Storm-Mathisen 1984). In this preparation, sIPSCs arise from axon terminals of TRN neurons (F1 terminals). As illustrated in Fig. 7A, in control conditions SNAP (500 µM) increased the sIPSC frequency with little apparent change in sIPSC amplitude (Fig. 7, A and B). After the addition of TTX (0.5 µM), the facilitation by SNAP persisted, but to a lesser extent than in control conditions (Fig. 7, A and B). This TTX-sensitive component within VB likely arises from suprathreshold excitation of TRN neurons (e.g., see Fig. 2A) that remain synaptically intact in the horizontal thalamic slice. As indicated in the cumulative probability plots, there was a significant decrease in the interevent intervals in the presence of SNAP in control and TTX conditions (Fig. 7C, P < 0.01, KS test). Similarly, the population data indicate that SNAP significantly increased the sIPSC frequency an average of 133.5 ± 7.5% of control (Fig. 6, D and E, P < 0.01, paired t-test) and in TTX, SNAP produced a peak increase in sIPSC activity that averaged 118.6 ± 4.8%, which was significantly greater than baseline levels (Fig. 6, D and E, P < 0.05, paired t-test, n = 9). Notable was a statistical difference of the SNAP-mediated frequency potentiation in TTX between LGN and VB relay cells (140.5 ± 16.0 vs. 118.6 ± 4.8%, P < 0.01). Unlike dLGN neurons, SNAP produced a significant increase in sIPSC amplitude in the control conditions (Fig. 6C, P < 0.01, KS test). The population data support the increase of sIPSC amplitude that averaged 109.0 ± 2.1% (Fig. 6, D and E, P < 0.01, paired t-test, n = 9), suggesting that a portion of increased sIPSCs resulted from suprathreshold depolarization of TRN neurons by SNAP.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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; McCauley et al. 2002, 2003). To summarize, we found that the NO donor SNAP or the NO precursor L-arginine significantly increased spontaneous GABA-mediated inhibitory activity in thalamic relay neurons by enhancing the frequency—but not the amplitude—of the IPSCs. The specific NO scavenger carboxyl-PTIO attenuated SNAP-mediated potentiation and the NOS inhibitor, L-NMMA acetate, decreased the L-arginine–mediated potentiation. These NO-mediated actions appear to be involved in an increase of the cGMP level because the soluble guanylyl cyclase inhibitor ODQ attenuated the SNAP-mediated potentiation. Furthermore, the increase in IPSC frequency was mimicked by the cGMP analogue 8-Br-cGMP, in the presence of the phosphodiesterase inhibitor IBMX. The augmentation of inhibitory activity by SNAP was present in both dLGN and VB relay neurons, but was significantly less in VB neurons. The VB nucleus, unlike the dLGN, lacks local circuit interneurons and receives most of its inhibitory innervation from TRN neurons. Thus our data indicate that NO leads to an increase in GABA release from presynaptic terminals of TRN neurons and likely local circuit neurons as well, thereby increasing the inhibitory drive onto thalamic relay neurons. cGMP dependency of presynaptic NO actions
Based on our results, the NO-mediated increase in inhibitory activity results from an increase in GABA release by presynaptic mechanisms. In our experiments, the sIPSC frequency was significantly increased by NO agonists; however, the sIPSC amplitude was unaltered. Furthermore, the increase in sIPSC frequency persisted in TTX, indicating suprathreshold excitation of presynaptic GABA-containing neurons (i.e., TRN neurons) was not required. Such a presynaptic mechanism is consistent with the NO actions reported in other brain regions including paraventricular nucleus of the hypothalamus, supraoptic neurons, nucleus accumbens, cultured neocortical neurons, and retinal neurons (Kraus and Prast 2002; Li et al. 2002; Ohkuma et al. 1998; Ozaki et al. 2000; Yu and Eldred 2005). Most NO-mediated actions described thus far in the CNS involve either cGMP or S-nitrosylation (Ahern et al. 2002) and our results appear dependent on the cGMP pathway. The cGMP analogue 8-Br-cGMP, in presence of the phosphodiesterase inhibitor IBMX, increased sIPSC frequency and the SNAP-mediated increase in sIPSC activity was inhibited by the guanylyl cyclase inhibitor ODQ.
The increase in cGMP produced by NO can target cGMP-gated channels (Ingram and Williams 1996; Zagotta and Siegelbaum 1996), cGMP-dependent phosphodiesterases (Kraus and Prast 2002), and cGMP-dependent PKG (Jaffrey and Snyder 1995). Despite the presence of type II cyclic GMP-dependent PKG within thalamic neurons, the selective inhibitor Rp-pCPT-cGMP did not attenuate the SNAP-mediated actions (Bladen et al. 1996). Furthermore, the increase in inhibitory activity also persisted in the presence of the phosphodiesterase inhibitor IBMX. Assuming the lack of PKG and phosphodiesterase involvement, one possible mechanism is that cGMP directly activates cGMP-gated channels in the presynaptic terminal, leading to transmitter release. One candidate is the hyperpolarization-activated mixed-cation current Ih; the HCN channels that mediate Ih have binding sites for cGMP and cAMP (Zagotta et al. 2003). Moreover, Ih contributes to increased GABA release in presynaptic terminals of cerebellar basket cells (Southan et al. 2000). Therefore the increase in cGMP produced by NO could potentiate HCN channels in the axon terminals or dendrite of inhibitory neurons (TRN and dLGN interneuron), leading to the increase of GABA release. However, at this point, we cannot definitively exclude the role of PKG because our highest Rp-pCPT-cGMP concentration tested (5 µM) may not completely block all PKG-mediated activities, although a lower concentration (1 µM) was used to completely block SNAP-mediated inhibitory actions in a slice preparation of rat paraventricular nucleus (Li et al. 2004). Furthermore, the cGMP pathway also appears to be involved in the postsynaptic depolarization of dLGN thalamic relay neurons by NO and the facilitation of excitatory synaptic responses arising from corticogeniculate afferents (Alexander et al. 2006; Pape and Mager 1992; Shaw et al. 1999). However, it is important to note the negligible effects of 8-Br-cGMP reported from in vivo single-unit recordings in cat dLGN, suggesting potential diversity in NO-mediated actions in the thalamus (Cudeiro et al. 1994).
Sources and target sites of NO in the thalamus
One potential source of NO in the thalamus arises from acetylcholine-containing brain stem nuclei. Cholinergic neurons arising from the parabrachial region of the brain stem that innervate dLGN also contain NOS (Carden et al. 2000; Erisir et al. 1997). Activity of the parabrachial neurons is positively correlated with arousal levels and therefore increased levels of NO-mediated actions may be correlated with increasing arousal levels (Williams et al. 1997). In addition, these cholinergic neurons also innervate presynaptic GABA-containing dendrites of dLGN interneurons that form dendrodendritic synapses onto relay cell dendrites, often forming a characteristic "triadic" junction (F2 terminal) (Famiglietti Jr and Peters 1972; Guillery 1969; Hamos et al. 1985; Montero 1986; Ralston 1971). Thus NO may provide an effective output control of presynaptic dendrites of local interneurons (Cox and Sherman 2000; Govindaiah and Cox 2004). Another possible source of NO is from GABA-containing neurons in the thalamus. NOS and GABA are co-localized in a subpopulation of local inhibitory interneurons in the cat dLGN (Erisir et al. 1997; McCauley et al. 2003).
Considering the innervation of TRN by cholinergic neurons of the parabrachial region, the TRN is another site for NO-mediated actions. In addition, recent evidence indicates that NOS is also expressed in TRN of ferrets (McCauley et al. 2002). Our data indicate that increased NO activity leads to depolarization of TRN neurons (Fig. 2) and increased GABA release from presynaptic terminals of TRN neurons (Fig. 7). These experiments are the first electrophysiological observations suggesting that TRN neurons may be a target for endogenous NO. The activation of TRN neurons plays an important role in oscillations of thalamocortical systems shown during the sleep cycle (Cox et al. 1997b; McCormick 2002; Steriade et al. 1993; von Krosigk et al. 1993). Furthermore, NO is also an easy diffusible substance that can reach several hundred microns (Garthwaite and Boulton 1995; Park et al. 1998), presumably acting as a spatial signal simultaneously influencing a large neuronal population by local diffusion in thalamus. Therefore the widespread effects for functional control of neural networks without direct synaptic connections could be indicative of NO action in thalamus. These properties may endow the NO system with important functions in controlling sensory transfer and thalamic oscillatory activity in a global manner.
Functional role of NO in the visual thalamus
Considering GABA-mediated inhibition can have important influences on visual information processing in the thalamus, alterations in inhibitory activity by NO could significantly influence such processing. GABA-mediated inhibition was previously reported to be involved in accurate discrimination of incoming signals and enhancing sensitivity for local contrast information (Berardi and Morrone 1984; Govindaiah and Cox 2004; Holdefer et al. 1989; Livingstone and Hubel 1981; Norton and Godwin 1992; Sillito and Kemp 1983). GABA-mediated activity appears to regulate receptive field sensitivity (Holdefer et al. 1989; Norton et al. 1989). Lesions of TRN neurons increase receptive field size in somatosensory thalamic neurons, suggesting a surround antagonistic role of TRN neurons (Lee et al. 1994). The increment of contrast caused the increasing response of LGN target cells using extracellular single-unit recording (Kaplan et al. 1987). From this, we would predict that the inhibitory action of NO could play an important role on contrast information by regulating receptive field size and/or sensitivity.
Previous in vivo studies indicate that NO leads to an enhancement of sensory-evoked responses in presumed thalamic relay neurons (Cudeiro et al. 1994; Shaw et al. 1999). Although there is some controversy regarding the role of cGMP underlying the facilitation, Shaw et al. (1999) found a striking similarity between the actions of NO agonists and cGMP, whereas Cudeiro et al. (1994) found negligible actions of cGMP activation. In vitro studies found postsynaptic depolarizations produced by NO agents in thalamic relay neurons, consistent with the excitatory effects of NO (Pape and Mager 1992). Our data provide a novel role of NO within the thalamus—that is, activation of NO by a cGMP-dependent pathways leads to a presynaptic enhancement of inhibitory activity that occurs independent of the action potential discharge of GABA-containing neurons. Depending on the spatial distribution of NO, such changes may provide a mechanism to sharpen the excitatory relay through the thalamus. Our working hypothesis is that with attentive states, increased output of NOS-containing cholinergic neurons would lead to increased NO synthesis and release, thereby leading to a direct postsynaptic depolarization decreasing the threshold for suprathreshold excitation through the thalamic relay and, at the same time, NO would lead to increased inhibitory activity that would in turn enhance surround antagonistic actions, ultimately increasing the signal-to-noise ratio and potentially sharpening receptive fields. Therefore we would speculate that NO may be crucial for sharpening visual transmission through potentiation of GABA release accompanied with the facilitation of sensory transmission.
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GRANTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODSRESULTSDISCUSSIONGRANTSACKNOWLEDGMENTSREFERENCES |
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FOOTNOTES |
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Address for reprint requests and other correspondence: C. L. Cox, Department of Molecular and Integrative Physiology, University of Illinois, 2357 Beckman Institute, 405 North Mathews, Urbana, IL 61801 (E-mail: cox2{at}uiuc.edu)
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