Input-selective potentiation and rebalancing of primary sensory cortex afferents by endogenous acetylcholine.

Acetylcholine (ACh) plays important roles in the modulation of activity and plasticity of primary sensory cortices, thus influencing sensory detection and integration. We examined this in urethane-anesthetized rats, comparing cholinergic modulation of short latency, large amplitude field postsynaptic potentials (fPSPs) in the visual cortex (V1) evoked by stimulation of the ipsilateral lateral geniculate nucleus (LGN), reflecting direct thalamocortical inputs, with longer latency, smaller amplitude fPSPs elicited by contralateral LGN stimulation, reflecting indirect, polysynaptic inputs. Basal forebrain (BF) stimulation (100 Hz) produced a significant (approximately 45%), gradually developing potentiation of the smaller, contralateral fPSPs, while ipsilateral fPSPs showed less enhancement (approximately 15%), shifting the relative strength of dominant/ipsi- and weaker/contralateral inputs to V1. Systemic or local, cortical blockade of muscarinic receptors (scopolamine) reduced potentiation of contralateral fPSP without affecting ipsilateral enhancement, thus preventing the relative amplification of contralateral inputs following BF stimulation. Systemic nicotinic receptor blockade (mecamylamine) resulted in depression of ipsilateral, and reduced enhancement of contralateral fPSPs after BF stimulation. N-methyl-D-aspartate receptor blockade (systemic MK-801) abolished ipsilateral fPSP enhancement without affecting contralateral potentiation. Neither drug reduced the amplification of contralateral relative to ipsilateral signals in V1. In a second experiment in the barrel cortex, BF stimulation enhanced multiunit activity elicited by whisker deflection in a muscarinic-sensitive manner. Similar to the observations in V1, this effect was more pronounced for weaker multiunit activity driven by a surround whisker than activity following principal whisker deflection. These experiments demonstrate that ACh release following BF stimulation exerts surprisingly selective effects to amplify non-dominant inputs to sensory cortices. We suggest that, by diminishing the imbalance between different afferent signals, ACh release during states of behavioral activation acts to induce a long-lasting facilitation of the detection and/or integration of signals in primary sensory fields of the cortical mantle.

Inactivation of prefrontal cortex abolishes cortical acetylcholine release evoked by sensory or sensory pathway stimulation in the rat.

Sensory stimulation and electrical stimulation of sensory pathways evoke an increase in acetylcholine release from the corresponding cortical areas. The pathways by which such sensory information reaches the cholinergic neurons of the basal forebrain that are responsible for this release are unclear, but have been hypothesized to pass through the prefrontal cortex (PFC). This hypothesis was tested in urethane-anesthetized rats using microdialysis to collect acetylcholine from somatosensory, visual, or auditory cortex, before and after the PFC was inactivated by local microdialysis delivery of the GABA-A receptor agonist muscimol (0.2% for 10 min at 2 microl/min). Before PFC inactivation, peripheral sensory stimulation and ventral posterolateral thalamic stimulation evoked 60 and 105% increases, respectively, in acetylcholine release from somatosensory cortex. Stimulation of the lateral geniculate nucleus evoked a 57% increase in acetylcholine release from visual cortex and stimulation of the medial geniculate nucleus evoked a 72% increase from auditory cortex. Muscimol delivery to the PFC completely abolished each of these evoked increases (overall mean change from baseline = -7%). In addition, the spontaneous level of acetylcholine release in somatosensory, visual, and auditory cortices was reduced by 15-59% following PFC inactivation, suggesting that PFC activity has a tonic facilitatory influence on the basal forebrain cholinergic neurons. These experiments demonstrate that the PFC is necessary for sensory pathway evoked cortical ACh release and strongly support the proposed sensory cortex-to-PFC-to-basal forebrain circuit for each of these modalities.

Modality- and region-specific acetylcholine release in the rat neocortex.

The basal forebrain is the major source of acetylcholine in the neocortex, and this projection has been variously described as either diffuse or highly specific. We used in vivo microdialysis to examine this discrepancy by collecting acetylcholine release simultaneously from visual, somatosensory and prefrontal cortical areas. Urethane-anesthetized rats were presented with visual and somatosensory stimulation in counter-balanced order and acetylcholine was measured using HPLC. Evoked acetylcholine release was modality-specific, i.e. visual stimulation evoked a large (75%) increase from visual cortex and little (24%) change from the somatosensory area whereas skin stimulation had the opposite effect. No increase was apparent in prefrontal cortex with either stimulation protocol. This experiment extends early studies using cortical cups to collect acetylcholine, and is consistent with the concept of functional specificity within the cholinergic basal forebrain with respect to both its sensory inputs and projections to the neocortex. This functional specificity within the cholinergic basal forebrain might be utilized in the modulation of different cortical regions during selective attention and plasticity.

Changes in corticothalamic modulation of receptive fields during peripheral injury-induced reorganization.

The influence of corticothalamic projections on the thalamus during different stages of reorganization was determined in anesthetized raccoons that had undergone previous removal of a single forepaw digit. Single-unit recordings were made from 522 sites in the somatosensory nucleus of the thalamus (ventroposterior lateral nucleus) before and after lesioning parts of primary somatosensory cortex. In those parts of ventroposterior lateral nucleus that had intact input from the periphery, the cortical lesion resulted in an immediate 85% increase in receptive field (RF) size. In animals studied 2-6 weeks after digit amputation, peripherally denervated thalamic neurons had unique RFs that were larger than normal, and these were not further enlarged by cortical lesion. However, at longer periods of reorganization (>4 mo), when the new RFs of denervated neurons had decreased in size, cortical lesion again produced expansion of RF size. These data demonstrate that corticothalamic fibers modulate the spatial extent of thalamic RFs in intact animals, probably by controlling intrathalamic inhibition. This corticothalamic modulation is ineffective during the early stages of injury-induced reorganization when new RFs are being formed, but is reinstated after the new RFs have become stabilized. The fact that neurons in the denervated thalamic region retained their unique RFs after cortical lesion indicates that their new inputs are not being relayed from a reorganized cortex and support the view that some plasticity occurs in or below the thalamus.

Cortical acetylcholine release and electroencephalogram activation evoked by ionotropic glutamate receptor agonists in the rat basal forebrain.

To determine the sensitivity of basal forebrain cholinergic neurons to ionotropic glutamate receptor activation, acetylcholine was collected from the cerebral cortex of urethane-anesthetized rats using microdialysis while monitoring cortical electroencephalographic (EEG) activity. alpha-Amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA; 1, 10, or 100 microM), N-methyl-D-aspartate (NMDA; 100 or 1000 microM) or a combination of AMPA (10 microM) and NMDA (100 microM) was administered to the basal forebrain using reverse microdialysis. Both glutamate receptor agonists produced concentration-dependent, several-fold increases in acetylcholine release indicating that they activated basal forebrain cholinergic neurons; AMPA was more potent, increasing acetylcholine release at a lower concentration than NMDA. The combination of AMPA and NMDA did not produce any greater release than each drug alone, indicating that the effects of these two drugs on cholinergic neurons are not additive. EEG was analyzed by fast Fourier transforms to determine the extent of physiological activation of the cortex. The highest concentrations of AMPA and NMDA tested produced small (25%) but significant increases in high frequency activity. There was a positive correlation across animals between the increases in power in the beta (14-30 Hz) and gamma (30-58 Hz) ranges and increases in acetylcholine release. These results indicate that glutamate can activate cholinergic basal forebrain neurons via both AMPA and NMDA ionotropic receptors but has a more modest effect on EEG activation.

Corticocortical inhibition of peripheral inputs within primary somatosensory cortex: the role of GABA(A) and GABA(B) receptors.

A conditioning-test pulse paradigm was used in combination with microiontophoresis to examine the corticocortical modulation of somatosensory processing. Single-cell recordings were made in the glabrous digit representation of primary somatosensory (S1) cortex in anesthetized raccoons. Test stimulation of the periphery (the on-focus digit) was preceded by conditioning stimulation of the cortical area that represents an adjacent digit at interstimulus intervals ranging from 5 to 200 ms. An early and prolonged inhibitory modulation was produced in most of the 61 neurons examined, and an early facilitation followed by inhibition was produced in about one-third of the cells. Microiontophoretic administration of a potent GABA(B) receptor antagonist, CGP 55845, blocked the inhibition and in many cases revealed a facilitation of the sensory response. Microiontophoretic administration of a GABA(A) receptor antagonist, gabazine, blocked inhibition at short interstimulus intervals and reduced the longer inhibition by half. These results indicate that connections between glabrous digit representations within S1 cortex produce predominantly inhibitory modulation of sensory input and that both GABA(A) and GABA(B) receptors contribute to this modulation. The relevance of these connections to the effects of peripheral nerve injury and subsequent reorganization is discussed.

Interactions between inputs from adjacent digits in somatosensory thalamus and cortex of the raccoon.

Interactions between somatosensory afferents arriving from different points in the periphery play an important role in sensory discrimination and also provide the substrate for plasticity following peripheral injury. To examine the extent and time course of such interactions, extracellular recordings were made from neurons in the primary somatosensory cortex and the ventroposterior lateral thalamus of anesthetized raccoons. Interactions between adjacent digits were studied using the conditioning-test paradigm in which a test pulse was delivered to the digit containing the neuron's receptive field (the on-focus digit) at various intervals following conditioning stimulation of an adjacent, off-focus digit. Off-focus stimulation produced predominantly inhibition of the test response with a maximum effect at 20-40 ms in both cortex and thalamus. The mean inhibition was approximately twice as large in the thalamus as in the cortex. Recordings were made in other animals after unmyelinated C fibers had been destroyed in the on-focus digit by subcutaneous injection of capsaicin. This resulted in a doubling of the responses evoked by the test stimulus in both regions, but the spontaneous discharge rate was not changed. The amount of inhibition produced in the cortex was unchanged by capsaicin treatment, but was reduced in the thalamus compared to control animals. This indicates that capsaicin-sensitive peripheral afferents provide a tonic control over interdigit inhibition in the thalamus.

Effect of GABAB receptor blockade on receptive fields of raccoon somatosensory cortical neurons during reorganization.

Single unit recordings were made in the fourth digit representation of raccoon somatosensory cortex after amputation of the fourth digit. The receptive fields of neurons in this "reorganized" cortex were studied before and after microiontophoretic application of a highly specific GABA(B) receptor antagonist, CGP 55845. When the recordings were performed early in the reorganization process, 3-5 weeks after amputation, CGP 55845 produced a greater expansion of the receptive field (184%) than at longer post-amputation intervals (17-34 weeks, 137% increase) or previously reported in intact animals (105%). Most of the receptive fields in these animals were restricted to either an adjacent digit or the palm and the expansion was adjacent to the predrug receptive field. However, in some cases block of GABA(B) receptors unmasked new responsive areas that were separated from the predrug field. In addition, GABA(B) receptor block often revealed higher threshold fields on an adjacent digit or palm. These results reinforce previous studies that used a GABA(A) receptor antagonist, and together they reveal the importance of GABAergic synapses in regulating the various inputs to cortical somatosensory neurons during reorganization.

Comparison of receptive field expansion produced by GABA(B) and GABA(A) receptor antagonists in raccoon primary somatosensory cortex.

Recordings were made from 62 neurons in the forepaw representation of primary somatosensory cortex in anesthetized raccoons. Microiontophoretic administration of a specific GABA(B) receptor antagonist, CGP 55845, produced receptive field expansion in 74% of 46 neurons, in which it was tested first. The mean receptive field area was approximately doubled, with increases ranging from 12 to 500%. The GABA(B) receptor agonist baclofen reduced the receptive field in most (11 of 16) neurons, but increased the size in 4 neurons. Comparison of the effects of GABA(B) and GABA(A) antagonists in the same cells showed that GABA(A) receptor blockade produced greater expansion than GABA(B) blockade (144% vs 114%, respectively). Simultaneous administration of the two antagonists produced additional expansion in 16 of 25 neurons. There was no evidence of separate skin regions being masked by the two GABA receptor subtypes, as the larger expansion usually included the skin that was unmasked by the less effective drug. These results indicate that both GABA(B) and GABA(A) receptors play a role in shaping the normal receptive fields in somatosensory cortex.

Postsynaptic dorsal column and cuneate neurons in raccoon: comparison of response properties and cross-correlation analysis.

The responses of 111 postsynaptic dorsal column (PSDC) neurons in the cervical spinal cord and 51 cuneate neurons with receptive fields on the glabrous skin of the forepaw were studied in anesthetized raccoons using extracellular recording techniques. The PSDC neurons had larger receptive fields than the cuneate neurons, but in both groups the fields never extended onto hairy skin. PSDC and cuneate neurons had approximately the same mean latency to electrical stimulation of the receptive field, but PSDC neurons had significantly lower thresholds. The majority of both PSDC and cuneate neurons also responded to electrical stimulation of an adjacent digit, even though they did not respond to mechanical stimulation of that digit. Cross-correlation analysis of the activity of 51 pairs of PSDC and cuneate neurons recorded simultaneously revealed a significant interaction in 26 pairs during spontaneous activity. In 20 of these neuron pairs, the probability that the cuneate neuron would fire was greater after the PSDC neuron had fired (suggesting a spinocuneate interaction), five pairs showed an interaction in the opposite (cuneospinal) direction, and one pair had a significant inhibitory interaction. These interactions occurred more often when the receptive fields of the two neurons were overlapping than when their fields were on adjacent digits. Frequency response analysis revealed greater coherence for those pairs showing a spinocuneate interaction than for those with a cuneospinal interaction. These results support the hypothesis that the PSDC system exerts a tonic facilitatory effect on cuneate neurons and that there may be some somatotopic organization to the interactions. However, the similar response latencies of the two groups of neurons makes it unlikely that PSDC neurons could contribute to the rapid initial processing of cutaneous information by the cuneate nucleus.

Role of inhibition in cortical reorganization of the adult raccoon revealed by microiontophoretic blockade of GABA(A) receptors.

Cortical reorganization was induced by amputation of the 4th digit in 11 adult raccoons. Animals were studied at various intervals, ranging from 2 to 37 wk, after amputation. Recordings were made from a total of 129 neurons in the deafferented cortical region using multibarrel micropipettes. Several types of receptive fields were described in reorganized cortex: restricted fields were similar in size to the normal receptive fields in nonamputated animals; multi-regional fields included sensitive regions on both adjacent digits and/or the underlying palm and were either continuous over the entire field or consisted of split fields. The proportion of neurons with restricted fields increased with time after amputation and was greater than previously found in subcortical regions. A GABA(A) receptor antagonist (bicuculline methiodide), glutamate, and GABA were administered iontophoretically to these neurons while determining their receptive fields and thresholds. Bicuculline administration resulted in expansion of the receptive field in 60% of the 93 neurons with cutaneous fields. In most cases (33 neurons) this consisted of a simple expansion around the borders of the predrug receptive field, and the average expansion (426%) was not different from that seen in nonamputated animals. In some neurons (n = 4), bicuculline produced an expansion from one digit onto the adjacent palm or another digit, an effect never seen in control animals. Bicuculline also changed the split fields of seven neurons into continuous fields by exposing a responsive region between the split fields. Finally, bicuculline changed the internal receptive field organization of 10 neurons by revealing subfields with reduced thresholds. In contrast to the situation in nonamputated animals, iontophoretic administration of glutamate also produced receptive field expansion in some neurons (n = 6), but the size and/or shape of the change was different from that produced by bicuculline, indicating that the effects of bicuculline were not due to an overall facilitation of neuronal activity. These results are consistent with the hypotheses that an important component of long-term cortical reorganization is the gradual reduction in effective receptive field size and that intracortical inhibitory networks are partially responsible for these changes.

Expansion of receptive fields in raccoon somatosensory cortex in vivo by GABA(A) receptor antagonism: implications for cortical reorganization.

The effect of antagonism of GABA(A) receptors on the receptive fields of raccoon primary somatosensory cortical neurons was tested using microiontophoretic administration of bicuculline methiodide (BMI). The size of cutaneous receptive fields was examined using minimal suprathreshold mechanical stimulation before, during, and after BMI administration. In 65 of 102 rapidly adapting neurons, BMI produced a clear expansion of the receptive field. The mean increase in receptive-field size was 286%. The receptive fields on the distal digit, which were initially smaller, showed smaller increases in absolute area than more proximal receptive fields, but the percentage increase did not vary with location. Greater expansion was seen in superficially located neurons than in those below 800 microm. Of particular significance was the finding that the expansion of receptive fields produced by BMI never extended from one digit onto an adjacent digit or onto the palm, even when the original receptive field was at the base of a digit. This finding indicates that intracortical GABAergic inhibition is insufficient to explain cortical reorganization following digit amputation.

Time course and effective spread of lidocaine and tetrodotoxin delivered via microdialysis: an electrophysiological study in cerebral cortex.

Microdialysis is a useful tool for administering drugs into localized regions of brain tissue, but the diffusion of drugs from the probe has not been systematically examined. Lidocaine (10%) and tetrodotoxin (TTX, 10 microM), drugs typically used in neural inactivation studies, were infused through a microdialysis probe into raccoon somatosensory cortex while evoked responses were recorded at four electrodes equally spaced 0.5--2.0 mm from the probe. The decreases in evoked response amplitude as a function of time and distance from the probe were used as functional measures to describe the time course and spread of the drugs. TTX inactivated distant sites more quickly and to a greater extent than lidocaine. Responses recovered within approximately 40 min after termination of lidocaine, but did not recover for at least 2 h after TTX. Based on these measurements, we estimated that, at the concentrations used, lidocaine has a maximal spread of 2.1 mm, while TTX could spread as far as 4.8 mm from the microdialysis probe. However, in terms of significant inactivation of neuronal activity, lidocaine and TTX have an effective spread of 1 and 2 mm, respectively.

The role of acetylcholine in cortical synaptic plasticity.

This review examines the role of acetylcholine in synaptic plasticity in archi-, paleo- and neocortex. Studies using microiontophoretic application of acetylcholine in vivo and in vitro and electrical stimulation of the basal forebrain have demonstrated that ACh can produce long-lasting increases in neural responsiveness. This evidence comes mainly from models of heterosynaptic facilitation in which acetylcholine produces a strengthening of a second, noncholinergic synaptic input onto the same neuron. The argument that the basal forebrain cholinergic system is essential in some models of plasticity is supported by studies that have selectively lesioned the cholinergic basal forebrain. This review will examine the mechanisms whereby acetylcholine might induce synaptic plasticity. It will also consider the neural circuitry implicated in these studies, namely the pathways that are susceptible to cholinergic plasticity and the neural regulation of the cholinergic system.

Antibody for human p75 LNTR identifies cholinergic basal forebrain of non-primate species.

192-IgG is an antibody directed against the p75 low affinity nerve growth factor receptor in rats, whereas ME 20.4 was raised against the analogous protein in humans. Coupled to saporin, 192-IgG and ME 20.4 have been used to lesion basal forebrain neurons in rats and primates, respectively. We compared the cross-reactivity of 192-IgG and ME 20.4 in the basal forebrain of rat, human, dog, cat, raccoon, pig, and rabbit. We found excellent species cross-reactivity of ME 20.4 in dog, raccoon, cat, pig and rabbit. In contrast, 192-IgG did not label neurons in any species other than rat. Our findings suggest that ME 20.4-saporin could be used to produce cholinergic basal forebrain lesions in several non-primate species.

Inhibition of synaptically evoked cortical acetylcholine release by adenosine: an in vivo microdialysis study in the rat.

The release of cortical acetylcholine from the intracortical axonal terminals of cholinergic basal forebrain neurons is closely associated with electroencephalographic activity. One factor which may act to reduce cortical acetylcholine release and promote sleep is adenosine. Using in vivo microdialysis, we examined the effect of adenosine and selective adenosine receptor agonists and antagonists on cortical acetylcholine release evoked by electrical stimulation of the pedunculopontine tegmental nucleus in urethane anesthetized rats. All drugs were administered locally within the cortex by reverse dialysis. None of the drugs tested altered basal release of acetylcholine in the cortex. Adenosine significantly reduced evoked cortical acetylcholine efflux in a concentration-dependent manner. This was mimicked by the adenosine A(1) receptor selective agonist N(6)-cyclopentyladenosine and blocked by the selective A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The A(2A) receptor agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenosi ne hydrochloride (CGS 21680) did not alter evoked cortical acetylcholine release even in the presence of DPCPX. Administered alone, neither DPCPX nor the non-selective adenosine receptor antagonist caffeine affected evoked cortical acetylcholine efflux. Simultaneous delivery of the adenosine uptake inhibitors dipyridamole and S-(4-nitrobenzyl)-6-thioinosine significantly reduced evoked cortical acetylcholine release, and this effect was blocked by the simultaneous administration of caffeine. These data indicate that activation of the A(1) adenosine receptor inhibits acetylcholine release in the cortex in vivo while the A(2A) receptor does not influence acetylcholine efflux. Such inhibition of cortical acetylcholine release by adenosine may contribute to an increased propensity to sleep during prolonged wakefulness.

Innervation of the digit on the forepaw of the raccoon.

The innervation of the digits on the raccoon forepaw was examined by using immunochemistry for protein gene product 9.5, calcitonin-gene related peptide, substance P, neuropeptide-Y, tyrosine hydroxylase, and neurofilament protein. The larger-caliber axons in the ventral glabrous skin terminate as Pacinian corpuscles deep in the dermis, small corpuscles and Merkel endings around the base of dermal papillae, and Merkel endings on rete pegs in dermal papillae. Extensive fine-caliber innervation terminates in the epidermis and on the microvasculature. The innervation is more dense in the distal than in the proximal volar pads. Pacinian endings are also concentrated in the transverse crease separating the distal and proximal pads. In the dorsal hairy skin, hair follicles are well innervated with piloneural complexes. Merkel innervation is located under slight epidermal elevations and in some large Merkel rete pegs located at the apex of transverse skin folds just proximal to the claw. No cutaneous Ruffini corpuscles were found anywhere on the digit. The claw is affiliated with dense medial and lateral beds of Pacinian endings, bouquets of highly branched Ruffini-like endings at the transition from the distal phalanx and unmyelinated innervation in the skin around the perimeter. Encapsulated endings are located at the lateral edge of the articular surface of the distal phalanx. Extensive fine-caliber innervation is affiliated with sweat glands and with the vasculature and is especially dense at presumptive arteriovenous sphincters. Virtually all of the sweat gland and vascular innervation is peptidergic, whereas most of the unmyelinated epidermal innervation is nonpeptidergic.

Two distinct populations of cholinergic neurons in the septum of raccoon (Procyon lotor): evidence for a separate subset in the lateral septum.

The present study focused on cholinergic neurons in the lateral septal region of the raccoon detected by choline acetyltransferase (ChAT)-immunostaining. For comparison of the cholinergic neurons of the medial and lateral septal nuclei, soma sizes were measured, and several antibodies were applied that differentially characterize these cells in several species: low-affinity neurotrophin receptor p75 (p75(NTR)), calbindin-D(28k) (CALB), and constitutive nitric oxide synthase (cNOS). To compare the basic organization of the raccoon septum with that in other mammals, parvalbumin (PARV) immunocytochemistry and Wisteria floribunda-agglutinin (WFA) lectin histochemistry also were used in double-staining experiments. The ChAT-immunoreactive neurons of the rostral lateral septum are arranged in laminae. Accumulations of cholinergic varicosities, often clearly ensheathing noncholinergic neurons, occupy small territories of the rostral septum. Such regions become larger in the caudal septum. They are assumed to correspond to the septohippocampal and septofimbrial nuclei of the rat. In contrast to the large medial septal cholinergic neurons of the raccoon that contain p75(NTR), CALB, and cNOS, the cholinergic neurons of the lateral septum are smaller and do not express these markers. A further peculiarity is that the region of the lateral septum that contains cholinergic neurons corresponds to WFA-labelled extracellular matrix zones that contain chondroitin sulfate proteoglycans. In addition to clustered thread- or ring-like accumulations of the WFA, sparsely labelled perineuronal nets surround the lateral septal cholinergic neurons. Similar to other species that have been investigated, perineuronal nets are completely absent around cholinergic cells of the medial septum. The PARV-containing neurons of this region, however, are enwrapped by perineuronal nets as they are in the rat. Within the medial septum, the PARV-containing neurons are restricted to ventral bilateral territories that are devoid of cholinergic cells. In this respect, they differ from the more vertically arranged PARV-containing medial septal cells in rodents and primates. Apart from striking differences in numbers and distribution patterns, the raccoon lateral septal cholinergic neurons resemble those detected by Kimura et al. (Brain Res [1990] 533:165-170) in the ventrolateral septal region of rat and monkey. Their participation in the functions of the lateral septum remains to be elucidated.

The role of basal forebrain neurons in tonic and phasic activation of the cerebral cortex.

The basal forebrain and in particular its cholinergic projections to the cerebral cortex have long been implicated in the maintenance of cortical activation. This review summarizes evidence supporting a close link between basal forebrain neuronal activity and the cortical electroencephalogram (EEG). The anatomy of basal forebrain projections and effects of acetylcholine on cortical and thalamic neurons are discussed along with the modulatory inputs to basal forebrain neurons. As both cholinergic and GABAergic basal forebrain neurons project to the cortex, identification of the transmitter specificity of basal forebrain neurons is critical for correlating their activity with the activity of cortical neurons and the EEG. Characteristics of the different basal forebrain neurons from in vitro and in vivo studies are summarized which might make it possible to identify different neuronal types. Recent evidence suggests that basal forebrain neurons activate the cortex not only tonically, as previously shown, but also phasically. Data on basal forebrain neuronal activity are presented, clearly showing that there are strong tonic and phasic correlations between the firing of individual basal forebrain cells and the cortical activity. Close analysis of temporal correlation indicates that changes in basal forebrain neuronal activity precede those in the cortex. While correlational, these data, together with the anatomical and pharmacological findings, suggest that the basal forebrain has an important role in regulating both the tonic and the phasic functioning of the cortex.

Quantitative trait loci associated with resistance to Fusarium head blight and kernel discoloration in barley.

Resistance to Fusarium head blight (FHB), deoxynivalenol (DON) accumulation, and kernel discoloration (KD) in barley are difficult traits to introgress into elite varieties because current screening methods are laborious and disease levels are strongly influenced by environment. To improve breeding strategies directed toward enhancing these traits, we identified genomic regions containing quantitative trait loci (QTLs) associated with resistance to FHB, DON accumulation, and KD in a breeding population of F(4:7) lines using restriction fragment length polymorphic (RFLP) markers. We evaluated 101 F(4:7) lines, derived from a cross between the cultivar Chevron and an elite breeding line, M69, for each of the traits in three or four environments. We used 94 previously mapped RFLP markers to create a linkage map. Using composite interval mapping, we identified 10, 11, and 4 QTLs associated with resistance to FHB, DON accumulation, and KD, respectively. Markers flanking these QTLs should be useful for introgressing resistance to FHB, DON accumulation, and KD into elite barley cultivars.