1. The present studies investigated conditions for the induction of long-term potentiation (LTP) in the local horizontal pathways of layers II/III in the primary motor cortex (MI) of the adult rat. Field potential and intracellular recordings demonstrated synaptic interactions across the superficial layers within MI that could be enhanced transiently by focal application of the gamma-aminobuturic acid-A receptor antagonist bicuculline methiodide (Bic) at the recording site. 2. Field potentials evoked in the superficial MI horizontal pathways increased in amplitude after tetanizing, theta burst stimulation (TBS), but only when Bic was applied transiently at the recording site immediately before TBS. In the absence of Bic, TBS failed to produce long-lasting increases in horizontally evoked field responses. By contrast, TBS delivery during focal Bic application increased field potential amplitudes by 25-35% when measured 25-30 min after stimulation. The amount of potentiation was greater when two converging horizontal inputs were stimulated together but was not increased with higher intensity stimulation. Persistent effects of Bic application alone were evident. However, these effects were small unless Bic application continued until evoked field potential amplitude increase exceeded 200% of baseline. 3. The synaptic nature of field potential increases were confirmed using intracellular recordings of layer II/III neurons located near field potential electrodes. 4. LTP also could be induced without Bic application by cotetanization of vertical pathways simultaneously with horizontal activation. Vertical conditioning alone at 2 Hz, which affects inhibitory efficacy, was shown to transiently relieve depression of successive responses that ordinarily occurs during a burst of three horizontal stimuli. These results suggest that LTP of horizontal pathways may be regulated by spatiotemporal interactions between horizontal and vertical pathways. 5. Horizontal LTP was blocked reversibly by bath application of the N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovaleric acid, thereby implicating NMDA-receptor activation in LTP induction for these pathways. 6. The results confirm and extend our previous finding that the potential for activity-dependent modification of synaptic connections exists within the intrinsic horizontal connections of the superficial cortical layers. Synaptic modification across horizontally connected neurons appears to be regulated both by the arrangement of intrinsic circuitry and by the availability of mechanisms for modification at individual synapses. The properties of horizontal connections indicate that they form a spatial substrate and provide an activity-dependent mechanism for plasticity of adult cortical representations.

These experiments examined the ability of the adult motor cortex to reorganize its relationship with somatic musculature following nerve lesions. Cortical motor output organization was assessed by mapping the areal extent of movements evoked by intracortical electrical stimulation in anesthetized rats. Output patterns of the motor cortex of normal rats were compared with those of adult rats that had received either a forelimb amputation or a facial motor nerve transection 1 week to 4 months earlier. In both experimental conditions the extent of some representations increased. Stimulation thresholds required to elicit movements in expanded representations were at or below normal levels. After forelimb amputation, the area from which shoulder movements could be evoked at low thresholds enlarged. Sectioning of the branches of the facial nerve that innervate the vibrissa musculature enlarged the motor cortex forelimb and eye/eyelid output areas; these enlargements appeared to occupy the former vibrissa area. These results indicate that the amount of cortex controlling a group of muscles and the strength of the relationship between a cortical locus with its target muscles is modified by nerve lesions in adult mammals. They also show that motor nerve lesions are sufficient to produce this change and that the changes can appear as early as 7 days following a peripheral nerve injury.

Substantia nigra pars reticulata (SNr) neurons, antidromically activated following stimulation of the dorsal thalamus and/or superior colliculus were intracellularly stained with HRP. Light microscopic analysis revealed that the labeled SNr neurons have axon collaterals arborizing within SNr. Axon collaterals of SNr neurons partially overlapped with the dendritic fields of their parent cells and also extended beyond the parent dendritic fields. The labeled axon terminals did not closely appose the parent cell processes, suggesting that the collaterals most likely terminate on neurons other than the parent cell. Electrical stimulation of either the thalamus or the superior colliculus induced monosynaptic and polysynaptic IPSPs in SNr cells. The polysynaptic IPSPs evoked from thalamic stimulation disappeared following hemitransection of the brain just rostral to the thalamus while the monosynaptic IPSPs remained the same. Since there are no known afferents from either thalamus or superior colliculus to SNr, we consider that these monosynaptic IPSPs are due to activation of the recurrent collaterals of SNr projection cells. The results of this study indicate that projection neurons of SNr also have an inhibitory role within the SNr.

Somatotopic representation patterns in the motor cortex (MI) of rats that had a unilateral forelimb amputation on the first postnatal day were examined after 2-4 months of survival. Intracortical electrical stimulation and recording techniques were used to map the somatic representation in MI and in the somatic sensory cortex (SI). In normal rats, vibrissa, forelimb, and hindlimb areas comprise the bulk of the MI representation. Stimulation within the forelimb area elicits elbow, wrist, or digit movements at the lowest current intensities. The proximal limb representation appears to be contained within the distal forelimb area, since shoulder movements are nearly always evoked by stimulating at higher current intensities at some distal forelimb sites. In agreement with previous studies, the distal forelimb representation overlapped the adjacent part of the granular SI cortex. Following removal of the forelimb at birth, 3 novel features of MI organization were observed. First, the areas from which stimulation evoked movements of the vibrissa or the shoulder musculature were larger than normal. Stimulation thresholds were lower than those required for comparable movements in normal rats throughout these areas, suggesting that nerve section had not simply unmasked a high-threshold representation. Second, vibrissa movements were more commonly paired with movements of the proximal forelimb muscles at the same site. Third, stimulation in the adjacent granular SI cortex failed to evoke shoulder or trunk movements, although receptive-field mapping in this region showed that cells were responsive to cutaneous stimulation of the trunk and shoulder region. These results indicate that several organizational features develop differently in MI following perinatal nerve injury: certain remaining muscle groups have enlarged cortical representations, there is a strengthening of some normally weak connections from MI to the proximal musculature, and muscles are grouped in unusual combinations. These data demonstrate that the formation of MI representation patterns is strongly influenced by nerve injury during the perinatal period.