Threshold For Antidromic Activation Research Articles

Estradiol-sensitive projection neurons in the female rat preoptic area.

Electrical stimulation of the preoptic area (POA) interrupts the lordosis reflex, a combined contraction of back muscles, in response to male mounts and the major receptive component of sexual behavior in female rat in estrus, without interfering with the proceptive component of this behavior or solicitation. Axon-sparing POA lesions with an excitotoxin, on the other hand, enhance lordosis and diminish proceptivity. The POA effect on the reflex is mediated by its estrogen-sensitive projection to the ventral tegmental area (VTA) as shown by the behavioral effect of VTA stimulation as well as by the demonstration of an increased threshold for antidromic activation of POA neurons from the VTA in ovariectomized females treated with estradiol benzoate (EB). EB administration increases the antidromic activation threshold in ovariectomized females and neonatally castrated males, but not in neonatally androgenized females; the EB effect is limited to those that show lordosis in the presence of EB. EB causes behavioral disinhibition of lordosis through an inhibition of POA neurons with axons to the VTA, which eventually innervate medullospinal neurons innervating spinal motoneurons of the back muscle. The EB-induced change in the threshold or the axonal excitability may be a result of EB-dependent induction of BK channels. Recordings from freely moving female rats engaging in sexual interactions revealed separate subpopulations of POA neurons for the receptive and proceptive behaviors. Those POA neurons engaging in the control of proceptivity are EB-sensitive and project to the midbrain locomotor region (MLR). EB thus enhances lordosis by reducing excitatory neural impulses from the POA to the VTA. An augmentation of the POA effect to the MLR may culminate in an increased locomotion that embodies behavioral estrus in the female rat.

Electrophysiology of neurones projections from the rat A1 noradrenergic region to the medial preoptic/anterior hypothalamic area: lack of effect of the oestrous cycle on their excitability.

The neuronal excitability of presumed A1 noradrenergic neurones in the ventrolateral medulla (VLM) which directly project to the medial preoptic/anterior hypothalamic area was analysed in pro-oestrous and metoestrous female rats under urethane anaesthesia. No significant difference was detected between the two groups for the antidromic activation threshold, absolute refractory period, frequency of successful antidromic propagation into the somatodendritic membrane, duration of post-stimulus inhibition, or spontaneous firing rate of these neurones. These results do not support the idea that the neuronal somata of A1 noradrenergic neurones in the VLM show a pro-oestrous increase in excitability during the oestrous cycle, although limitations of the methodology employed do not completely rule out this possibility.

Comparative properties of excitatory and inhibitory inter-laminar neocortical axons

In recent years it has become increasingly clear that variations in voltage-gated channels, as well as highly diverse geometrical properties, shape the way axons conduct action potentials to their terminals. Numerous cell types in the mammalian neocortex form a dense network of connections, and the properties of their axons may have an effect on the processing performed by this network. We studied the conduction properties of local, inter-laminar axons emanating from regular-spiking (RS) pyramidal neurons and Martinotti type inhibitory neurons (MCs) in layer 5 of the mouse barrel neocortex by comparing the patterns of their antidromic activation from layer 1.Both types of axons had similarly slow conduction velocities (∼0.3 m/s), compatible with thin unmyelinated fibers. In addition, in both types of neurons, subthreshold changes of the somatic membrane potential affected the stimulus threshold for evoking an antidromic spike in layer 1, a distance of 600–800 μm. However, the axons differed considerably in their antidromic activation profiles. 1) The antidromic latency in RS neurons was highly consistent while some MCs display considerable activation-latency jitter; 2) RS neurons displayed a steeper increase in excitability to repeated 40 Hz stimulation; 3) RS neurons displayed a sharp, step-like antidromic activation threshold to both somatic voltage and stimulus intensity, while MCs displayed a gradual recruitment pattern. Morphological differences in the branching pattern of the two types of neurons may account for some of these distinctions. These results suggest differences among excitatory and inhibitory neocortical neurons in the computational tasks of their local axons.

Response Characterstics of Spinothalamic Tract Neurons That Project to the Posterior Thalamus in Rats

A sizeable number of spinothalamic tract axons terminate in the posterior thalamus. The functional roles and precise areas of termination of these axons have been a subject of recent controversy. The goals of this study were to identify spinothalamic tract neurons (STT) within the cervical enlargement that project to this area, characterize their responses to mechanical and thermal stimulation of their receptive fields, and use microantidromic tracking methods to determine the nuclei in which their axons terminate. Forty-seven neurons were antidromically activated using low-amplitude (< or =30 microA) current pulses in the contralateral posterior thalamus. The 51 points at which antidromic activation thresholds were lowest were surrounded by ineffective tracks indicating that the surrounded axons terminated within the posterior thalamus. The areas of termination were located primarily in the posterior triangular, medial geniculate, posterior and posterior intralaminar, and suprageniculate nuclei. Recording points were located in the superficial and deep dorsal horn. The mean antidromic conduction velocity was 6.4 m/s, a conduction velocity slower than that of other projections to the thalamus or hypothalamus in rats. Cutaneous receptive fields appeared to be smaller than those of neurons projecting to other areas of the thalamus or to the hypothalamus. Each of the examined neurons responded exclusively or preferentially to noxious stimuli. These findings indicate that the STT carries nociceptive information to several target nuclei within the posterior thalamus. We discuss the evidence that this projection provides nociceptive information that plays an important role in fear conditioning.

Synchronized Clusters of Action Potentials can Increase or Decrease the Excitability of the Axons of Magnocellular Hypothalamic Neurosecretory Cells

Extracellular recordings were made from supraoptic nucleus (SON) cells in urethane anaesthetized male rats in vivo. Two stimulating electrodes were positioned to activate the cells antidromically, one in the mid axon region of the cells and the other at the axon terminals. Trains of 5-20 just-subthreshold stimuli at 5 s intervals decreased the threshold for antidromic activation from both sites. Whereas neither single stimuli, nor the stimuli at the beginning of a train of 20 stimuli evoked antidromic action potentials, later action potentials did so. Paradoxically, trains of 20 just-suprathreshold stimuli increased the threshold for activation of both axons and terminals. In recordings from the same cells, stimuli were applied singly at 5 s intervals at an intensity which almost invariably evoked an antidromic action potential. Identical stimuli were then applied in trains of 20 stimuli at 50 Hz. After the first train, the initial stimulus pulses of the trains frequently fell below threshold. Following a conditioning train of five stimuli applied to one electrode, the period of decreased threshold (increased excitability) at the other electrode lasted less than 100 ms and the period of increased threshold (decreased excitability) after 12 trains of 20 stimuli lasted between 5 and 10 s. Both decreased and increased excitability were seen at axons and terminals of both putative oxytocin and vasopressin cells. Since the excitability changes were shown in vivo at frequencies encountered during recordings, it is likely that they influence the probability of spike propagation and hormone secretion under physiological conditions.

Thalamic stimulation largely elicits orthodromic, rather than antidromic, cortical activation in an auditory thalamocortical slice

Stimulation of the medial geniculate body in an auditory thalamocortical slice elicits a short-latency current sink in the middle cortical layers, as would be expected following activation of thalamocortical relay neurons. However, corticothalamic neurons can have axon collaterals that project to the middle layers, thus, a middle-layer current sink could also result from antidromic activation of corticothalamic neurons and their axon collaterals. The likelihood of thalamic stimulation activating corticothalamic neurons would be reduced substantially if the corticothalamic pathway was not well preserved in the slice, and/or if the threshold for antidromic activation was significantly higher than for orthodromic activation. To determine the prevalence and threshold of antidromic activation, we recorded intracellularly from day 14–17 mouse brain slices containing infragranular cortical neurons while stimulating the medial geniculate or thalamocortical pathway. Antidromic spikes were confirmed by spike collision and characterized according to spike latency ‘jitter’ and the ability to follow a high-frequency (100 Hz) stimulus train. The ability to follow a 100-Hz tetanus was a reliable indicator of antidromic activation, but both antidromic and orthodromic spikes could have low jitter. Thalamic stimulation produced antidromic activation in two of 69 infragranular cortical neurons (<3%), indicating the presence of antidromic activity, but implying a limited corticothalamic connection in the slice. Antidromic spikes in 13 additional neurons were obtained by stimulating axons in the thalamocortical pathway. The antidromic threshold averaged 214±40.6 μA (range 6–475 μA), over seven times the orthodromic threshold for medial geniculate-evoked responses in layer IV extracellular (28±5.4 μA) or intracellular (27±5.6 μA) recordings. We conclude that medial geniculate stimulation activates relatively few corticothalamic neurons. Conversely, low-intensity thalamic stimulation strongly activates thalamocortical neurons. Thus, at low-stimulus intensities, the auditory thalamocortical slice can be used to probe mechanisms of thalamocortical function with limited antidromic activation of corticothalamic neurons.

Physiological studies of spinohypothalamic tract neurons in the lumbar enlargement of monkeys.

Recent anatomic results indicate that a large direct projection from the spinal cord to the hypothalamus exists in monkeys. The aim of this study was to determine whether the existence of this projection could be confirmed unambiguously using electrophysiological methods and, if so, to determine the response characteristics of primate spinohypothalamic tract (SHT) neurons. Fifteen neurons in the lumbar enlargement of macaque monkeys were antidromically activated using low-amplitude current pulses in the contralateral hypothalamus. The points at which antidromic activation thresholds were lowest were found in the supraoptic decussation (n = 13) or in the medial hypothalamus (n = 2). Recording points were located in the superficial dorsal horn (n = 1), deep dorsal horn (n = 10), and intermediate zone (n = 4). Each of the 12 examined neurons had cutaneous receptive fields on the ipsilateral hindlimb. All neurons responded exclusively or preferentially to noxious stimuli, suggesting that the transmission of nociceptive information is an important role of primate SHT axons. Twelve SHT neurons were also antidromically activated from the thalamus. In all cases, the antidromic latency from the thalamus was shorter than that from the hypothalamus, suggesting that the axons pass through the thalamus then enter the hypothalamus. These results confirm the existence of a SHT in primates and suggest that this projection may contribute to the production of autonomic, neuroendocrine, and emotional responses to noxious stimuli in primates, possibly including humans.

Temporal coincidence between the excitation of ventromedial hypothalamic efferents and the induction of lordosis reflex in ovariectomized estrogen-primed rats.

The temporal changes in excitability in ventromedial hypothalamic neurons which project to the midbrain central gray caused by chronic estrogen exposure were measured in ovariectomized rats. In 66 urethane-anesthetized animals which had either no capsule, or had a capsule containing estrogen implanted for 24 h, 48 h, 72 h or 96 h, 189 antidromic action potentials were recorded in the ventromedial hypothalamus (VMN) in response to stimulation of the midbrain central gray (CG). The antidromic activation threshold was lower in 40 recordings made from the VMN in the 72-h or 96-h group than in 67 from the no-treatment, 24-h or 48-h group. The decrease in the threshold coincided with the emergence of the lordosis reflex. In a separate cohort of ovariectomized rats, any absence of estrogen for 2-48 h before and during the measuring abolished the neuronal as well as the behavioral effects at 72 h. The results suggest that the lordosis reflex induced by estrogen alone depends on the excitation of VMN efferents to the CG. In addition, the indispensability of estrogen at the time of electrophysiological and behavioral evaluation indicates that a certain direct neural action of estrogen is involved in the behavioral activation.

Electrophysiological evidence that spinomesencephalic neurons in the cat may be excited via spinocervical tract collaterals

Extracellular microelectrode recordings were made from spinomesencephalic tract (SMT) neurons in the lumbosacral spinal cord of cats anaesthetized with chloralose and paralysed with gallamine triethiodide. The SMT cells were antidromically fired from the posterolateral parts of the superior colliculus and the intercollicular region, were located in laminae IV to VIII, and had response properties and axonal conduction velocities similar to those described previously. The effects of stimulating the dorsolateral funiculus of the cervical cord at C3 and rostral C1, below and above the termination of spinocervical tract (SCT) axons in the lateral cervical nucleus, were examined on 33 SMT cells. The strength of stimulation was adjusted so that at C3 it was above threshold for antidromic activation of SCT cells and at C1 was below threshold for activation of the same cells. Seven (21%) SMT neurons were excited from C3 but not from C1. The remaining 26 (79%) were excited from both C3 and rostral C1 and 23 (70% of these) were excited significantly more from C3. That is, 91% of the total sample were either excited only from C3 or more strongly from C3 than from rostral C1. We discuss the possible neuronal systems involved and conclude that the greater excitatory effects from C3 are most likely due to antidromic activation of the SCT. The shortest latency effects from C3 indicate a monosynaptic linkage between SCT cells with the fastest axons and the SMT. The longer latency actions may be due to monosynaptic connexions from SCT cells with slower conducting axons, to di- or polysynaptic actions from SCT cells with fast axons, or a combination of both. SMT cells are another population of spinal neurons, in addition to postsynaptic dorsal column, spinothalamic and dorsal horn spinocerebellar neurons, which receive excitation via SCT collaterals.

Estrogen-excitable forebrain projections to the ventral premammillary nucleus of the female rat

Retrograde labels by Nuclear Yellow from the female rat ventral premammillary nucleus (PMv) were most numerous in the lateral septum (LS) and the preoptic area (POA) and spread laterally into the substantia innominata. Other labels were in the diagonal band nucleus, the substantia innominata and the bed nucleus of the stria terminalis. Constant-current, single-pulse electrical stimulation of the PMv in urethane-anesthetized ovariectomized rats elicited antidromic action potentials in the cingulate cortex, in addition to the structures that contained labeled neurons. In the LS or cingulate cortex, but not in the POA, estrogen decreased antidromic activation thresholds and shortened refractory periods. The PMv is a way station that relays estrogen-excitable septal, but not preoptic, effects. The PMv also contains fibers of passage that originate in estrogen-excitable cingulate neurons.

Thyrotropin-releasing hormone (TRH) has independent excitatory and modulatory actions on lamina IX neurons of lumbosacral spinal cord slices from adult rats.

Coronal and horizontal slices of the lumbar and sacral spinal cord, respectively, of ovariectomized adult rats, either treated with estrogen (OVX+E) or untreated (OVX), were used to test the neuronal actions of TRH and its metabolite, cyclo(His-Pro) (or cHP). Both coronal slices, which possess only short stumps of ventral roots (VRs), and horizontal slices, in which long sections of VRs were preserved, were used for extracellular recording of single motor and other types of neurons. Methodological comparisons between these two types of slices showed that the length of VRs preserved had no significant effect on the characteristics of motoneurons (MNs). In coronal slices, MNs in medial and lateral lamina IX (MNM and MNL, respectively) were identified by antidromic activation. Of these lumbar MNs, estrogen treatment lowered the antidromic activation threshold for MNM but not MNL. Because MNM innervate the back muscles crucial for the execution of the estrogen-dependent lordosis, the observed estrogen effect may contribute to the hormone's induction of the sexual behavior. The recorded MNs and other types of neurons were subjected to bath applications of TRH, cHP, and neurotransmitters. TRH was found to be capable of evoking an early, shorter-lasting neuronal excitation and/or a late, longer-lasting modulation of neuronal responses to transmitters. Each neuronal action could occur with or without the other, and the occurrence of the excitation did not affect the probability of whether a modulation would occur later. The modulatory, but not the excitatory, action appeared to be shared by cHP, because cHP could also modulate neuronal responses in similar, if not identical, ways as TRH did, but could neither stimulate neurons nor mimic TRH in desensitizing TRH-evoked excitation. The modulatory actions of the two peptides were not affected by estrogen. Although the excitatory action was desensitized by repeated TRH applications, the modulatory action did not appear to be attenuated but instead was often enhanced by repeated administrations of TRH and/or cHP. These results, together with the essentially identical findings from our previous study on hypothalamic neurons, indicate that the excitatory and the modulatory actions of TRH are independent of each other and, hence, are mediated by different subcellular mechanisms.

Effects of upper cervical spinal cord stimulation on neurons in the lumbosacral enlargement of the cat: spinothalamic tract neurons

Extracellular microelectrode recordings were made from deep spinothalamic tract neurons in the lumbosacral spinal cord of cats anaesthetized with chloralose and paralyzed with gallamine triethiodide. The effects of upper cervical spinal cord stimulation were tested on 43 spinothalamic tract neurons, by stimulation of the ipsilateral dorsolateral funiculus at C3 and rostral C1 using five or six shocks at 333 Hz. The strength of cervical stimulation was adjusted so that the C3 shock was above threshold for antidromic activation of spinocervical tract neurons but the same strength of shock applied at C1 was below threshold for the same neurons. Four of the 43 spinothalamic cells (9%) were not influenced by upper cervical stimulation. The remaining 39 spinothalamic tract cells (91%) were all excited from the upper cervical cord. Twenty-seven of these (63%) were excited more strongly from C3 than from C1, 4 (9%) were excited more strongly from C1 than from C3, and the remaining eight cells (19%) showed no significant differences between their responses to stimulation at C1 and C3. There were no obvious differences between those spinothalamic tract neurons showing differential effects from C1 and C3 and those showing no such effects. The neuronal systems possibly responsible for the differential effects from C3 and C1 on spinothalamic tract neurons are discussed. We conclude that the most likely candidate system for the greater excitation from C3 compared with C1 is the subset of spinocervical tract neurons with axon collaterals in the lumbosacral enlargement and that the spinothalamic tract is a further ascending path, in addition to the postsynaptic dorsal column path, that receives excitatory input from spinocervical axon collaterals. The greater excitation from C1 compared with C3 is interpreted as due to excitation from C1 and a mixture of excitation and inhibition from C3. The responsible neuronal systems seem likely to be either the spinocervical neurons with axon collaterals operating on the spinothalamic tract via inhibitory interneurons, or cells in the lateral cervical nucleus with axons descending to the lumbosacral cord.

Diametrically opposite effects of estrogen on the excitability of female rat medial and lateral preoptic neurons with axons to the midbrain locomotor region

Electrical stimulation of the midbrain locomotor region (MLR) in 76 ovariectomized, urethan-anesthetized female rats elicited antidromic action potentials in 252 preoptic neurons. Thresholds and refractory periods for the activation ranged from 60 to 1550 μA and 1.3 to 5.0 ms, respectively. The probability distribution for the peak-to-peak amplitude (2–14 mV) or the overall duration (0.7–4.4 ms) was bell-shaped, whereas that for the latency (1.8–33.5 ms) was distinctively bimodal with a division at 12.0 ms. Two groups of preoptic neurons of a similar soma size therefore project to the MLR presumably via different routes. In 121 neurons with latencies ≤12.0 ms, estrogen lowered the antidromic activation thresholds (nested analysis of variance, P < 0.02), but 131 neurons with latencies >12.0 ms had their thresholds increased ( P < 0.005) and refractory periods prolonged ( P < 0.02) by estrogen. Even though both overlapped in part, many potentials with the shorter latencies were recorded from the medial part of the lateral preoptic area (mLPO), lateral to the recording sites of the longer-latency potentials in the medial preoptic area (MPO). The observed antagonistic effects of estrogen on the two groups of preoptic neurons with axons to the MLR may contribute to increased locomotor activity in female rats in estrus.

Persistent increase of hippocampal presynaptic axon excitability after repetitive electrical stimulation: dependence on N-methyl-D-aspartate receptor activity, nitric-oxide synthase, and temperature.

The electrical excitability of Schaffer collateral axons and/or terminals was studied in hippocampal slices by monitoring single, CA3 pyramidal neurons activated antidromically from CA1 stratum radiatum. At 22 degrees C, weak, repetitive stimulation with as few as 10 impulses at 2 Hz led to a robust lowering of the antidromic activation threshold that lasted > 30 min. The effect was completely absent at 32 degrees C and was blocked by both the N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovalerate and the inhibitor of nitric-oxide synthase, L-nitro-arginine methyl ester. Such threshold lowering would alter the variance of synaptic responses from axons stimulated in the variable excitation region of their input-output functions. These results thus raise important doubts about the interpretation of experiments in which the so-called minimal-stimulation method has been used at reduced temperature to infer changes in quantal transmission during hippocampal long-term potentiation. In the present experiments, no changes were observed in the estimate of excitatory postsynaptic potential quantal content in long-term potentiation experiments at either temperature, which could not be accounted for by an artificial, temperature-dependent change in the responsiveness of presynaptic axons.

Physiological characterization of spinohypothalamic tract neurons in the lumbar enlargement of rats.

1. Ninety-six neurons in the lumbar enlargement of urethananesthetized rats were antidromically activated from the contralateral hypothalamus. The antidromic stimulating electrode was moved systematically within the hypothalamus until antidromic activation could be produced with currents of less than or equal to 50 microA (18.6 +/- 10.8 microA; mean +/- SD). The points at which antidromic activation thresholds were lowest were found in several regions of the hypothalamus but were concentrated in the optic tract and the supraoptic decussation. 2. The recording locations of 79 spinohypothalamic tract (SHT) neurons were marked and recovered. Twenty-nine were located in the superficial dorsal horn (SDH), 42 in the deep dorsal horn (DDH), 4 in the intermediate zone, and 2 in the gray matter surrounding the central canal. Two additional marks were located in the dorsal lateral funiculus (DLF). 3. The responses of 46 SHT neurons were examined during innocuous and noxious mechanical stimulation of their receptive fields. Forty-eight percent of recorded SHT neurons responded to both innocuous and noxious stimuli (wide dynamic range, WDR) and 39% responded only to noxious stimuli (high threshold, HT). Therefore 87% of SHT neurons responded preferentially or exclusively to noxious mechanical stimulation. Nine percent of SHT neurons responded exclusively to innocuous manipulation of joints and muscles. Four percent of SHT neurons responded only to innocuous tactile stimul (low threshold, LT). WDR, HT, and LT neurons were recorded widely throughout the dorsal horn; no relationship was found between the locations of recording sites in the dorsal horn and the response types of the neurons. SHT neurons that responded to stimulation of muscle, tendon, or joint were recorded deep in the gray matter. 4. The effects of heating the receptive fields were determined for 25 SHT neurons. Fourteen (56%) responded to thermal stimuli. Six (43%) of the responsive neurons responded at low frequencies to innocuous warming (38-41 degrees C) but more vigorously to noxious (greater than or equal to 45 degrees C) heating. The other eight responded only to noxious heat. Eighteen percent (3/17) of tested SHT neurons were activated by noxious cooling of their receptive fields. 5. Cutaneous receptive fields of most recorded SHT neurons were small, typically involving areas as small as two or three toes on the ipsilateral hindlimb; the largest receptive fields covered the entire paw. These findings indicate that relatively precise information about the location of innocuous and noxious stimuli is conveyed directly to the hypothalamus by SHT neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Somatosensory response properties of contralaterally projecting spinothalamic and nonspinothalamic neurons in the second cervical segment of the cat

1. The upper cervical spinal cord contains over one-third of the cells of the spinothalamic tract (STT). This study investigated response properties of contralaterally projecting STT neurons in C2 of the cat by the use of single-unit, microelectrode recordings. Standard antidromic stimulation and collision techniques were used to identify STT units projecting to the contralateral thalamus. Once an STT unit was found, its receptive field (RF) and responses to cutaneous stimuli such as touch, pressure, deep muscle squeeze, tap, noxious pinch, and heat were characterized. C2 units that were not activated from the contralateral thalamus (non-STT units) were also characterized. The locations of thalamic stimulation electrodes and spinal recording sites were reconstructed from electrolytic lesions. 2. A total of 48 STT and 68 non-STT units were well characterized. RF sizes were classified as small, intermediate, large, or whole body. Each unit was also classified as having one of two possible response types: simple units were those with homogeneous responses within the RF and were classified as low threshold (LT), high threshold (HT), wide dynamic range (WDR), deep, or tap. Complex units were those that responded differently in different regions of the RF. 3. The average depth of non-STT units subdivided by RF size was 2.1 +/- 0.6 (SD) mm for cells with small RFs, 2.4 +/- 0.8 mm for cells with intermediate RFs, 2.8 +/- 0.3 mm for cells with large RFs, and 2.7 +/- 0.5 mm for cells with whole-body RFs. The average depth of non-STT units based on response type was 2.0 +/- 0.5 mm for LT, 2.3 +/- 0.7 mm for HT, 2.1 +/- 0.7 mm for WDR, 2.6 +/- 0.9 mm for deep, 2.6 +/- 0.5 mm for tap, and 2.4 +/- 0.2 mm for complex. 4. A somatotopic organization along the rostrocaudal length of C2 and upper C3 was observed for non-STT units with small- and intermediate-size RFs. The average distance of the recording sites from the rostralmost dorsal rootlet of C2 was 3.8 +/- 2.1 mm for units with RFs on the face, 7.1 +/- 4.3 mm for units with RFs on the neck, and 11.9 +/- 5.1 mm for units with RFs on the forelimb. 5. The average threshold for antidromic activation of STT units was 175 +/- 120 microA. Most C2 STT units were activated from the ventroposterior region of the thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

The Characteristics of Medial Septal Neurons Antidromically Identified as Projecting to the Median Eminence and their Response to Gonadal Steroids

Abstract We have obtained extracellular single unit recordings from 129 neurons in the medial septum of the male rat that projected to the median eminence. These cells were identified on the basis of their antidromic responses to electrical stimulation in the median eminence. The antidromically-evoked spike was always followed by a period of inhibition (-100 ms) which often (80%) persisted at stimulus intensities below threshold for antidromic activation. The identified neurons displayed one of three patterns of activity, the relative proportions of which were dependent upon the anesthetic. In rats anesthetized with urethane, 15% of the antidromically identified septal neurons displayed an oscillating, 25% a continuous, and 61% a low irregular pattern of spontaneous activity or no activity. In contrast, in barbiturate-anesthetized animals only 6% exhibited an oscillating and 3% a continuous pattern of activity. The remaining neurons (91%) displayed either a low firing rate or were silent. We then assessed the responses of these identified neurons to systemic administration of gonadal steroids. Systemic administration of 17beta-estradiol elicited a rapid decrease in the firing rate of 9 of 29 neurons tested. The inhibitory response was specific to those cells displaying an oscillating (6/9) or continuous (3/6) firing pattern of which 60% were inhibited. In contrast, systemic administration of testosterone failed to elicit such changes in the activity of the identified septal neurons (n = 12) including one neuron which was subsequently shown to be inhibited by estradiol. As such identified septal neurons may contain gonadotropin-releasing hormone, these results suggest a role for estradiol but not testosterone in the short-term regulation of the secretion of this releasing hormone in the male rat.

Excitatory influence of the accessory olfactory bulb on tuberoinfundibular arcuate neurons of female mice and its modulation by oestrogen

The role of the accessory olfactory bulb in conveying pheromonal information to tuberoinfundibular arcuate neurons was examined electrophysiologically in chloral hydrate-anaesthetized, oestrogen (0.5 μg in silastic capsules)-treated and untreated ovariectomized Balb/c female mice. Electrical stimulation of the accessory olfactory bulb orthodromically excited part of tuberoinfundibular neurons which were antidromically stimulated from the median eminence and histologically verified as being located within the arcuate nucleus. No inhibitions followed accessory bulb stimulation. The excitatory response to accessory bulb stimulation was reversibly blocked by the local anaesthetic lignocaine infused into the amygdala. The percentage of tuberoinfundibular arcuate neurons responding to accessory bulb stimulation was significantly higher in oestrogen-treated than in untreated animals. There was no difference between the two groups for the antidromic activation threshold, spontaneous firing rate, absolute refractory period or frequency of successful antidromic propagation into the soma of tuberoinfundibular arcuate neurons. In oestrogen-treated preparations, tuberoinfundibular arcuate neurons responsive and unresponsive to accessory bulb stimulation could be distinguished by the frequency of successful antidromic propagation into the soma. These studies demonstrate that olfactory relay neurons in the accessory olfactory bulb act to enhance the activity of a subpopulation of tuberoinfundibular arcuate neurons via the amygdala and that this neural transmission is modulated by oestrogen.

Nerve growth factor-mediated sexual differentiation of the rat hypothalamus

Injection of antibody to nerve growth factor into the cerebral lateral ventricle blocked testosterone-induced behavioral defeminization of neonatal female rats. When tested as adults following ovariectomy and combined estrogen-progesterone treatment, the injected animals showed a significantly higher lordosis quotient than the testosterone-treated, normal rabbit serum-infused controls. Failure of vaginal opening and clitoral enlargement manifested the well-documented masculinizing effect of testosterone on the genitalia in the experimental as well as the control animals. Estrogen sensitivity of hypothalamic neurons which are responsible for the induction of lordosis was retained in the experimental animals. Recordings of the antidromic action potentials from neurons in the ventromedial nucleus of the hypothalamus following stimulation of the midbrain central gray revealed that estrogen decreased the antidromic activation threshold and shortened the absolute refractory period of the hypothalamic efferents along with the estrogen-induced behavioral activation in the experimental animals. In the control group, the estrogen-induced neuronal activation was lost altogether with the behavioral activation.

Cell size, projection path, and localization of estrogen-sensitive neurons in the rat ventromedial hypothalamus.

Antidromic action potentials were recorded in and around the ventromedial nucleus of the hypothalamus (VMN) of the ovariectomized female rat following stimulation of the central gray matter of the mesencephalon (CG). The animals had either the lateral or caudal trajectory of the VMN efferent disrupted by a small knife cut. Changes in the polarity, peak-to-peak amplitude, and the duration of the initial positive deflection of the antidromic action potentials were recorded for each response as the recording electrode was advanced at 10-micron intervals from the point of detection of the potential until its deterioration. Seventy-four recordings in which potentials exceeded 2 mV at the maxima were subjected to further analysis. The mean spatial spread of the extracellular antidromic action potentials, which was measured by moving the recording electrode at 10-micron intervals, was significantly larger in responses in 17 animals bearing the posterior knife cut (n = 41) than those in 15 animals with the lateral knife cut (n = 33). Mean peak-to-peak amplitude was also significantly greater in responses from the posterior-cut animals than in those from the lateral-cut ones. In the former, action potentials were completed with a shorter time lapse than the latter. In the posterior-cut animals, estrogen treatment of the ovariectomized rats significantly lowered antidromic activation thresholds and shortened absolute refractory periods for CG stimulation. Estrogen had no detectable effect on the excitability of cells that survived the lateral cut. Histological analyses located antidromically driven cells in the posterior-cut animals in the rostral extremity of the VMN and the adjacent retrochiasmatic area; those in the lateral-cut animals were scattered in and around the VMN, caudad to the former. These results suggest that rostral VMN neurons with large soma and laterally projecting axons are responsible for estrogen-dependent autonomic, neuroendocrine, and behavioral functions, such as reproduction and feeding.